Showing papers by "Gideon Koren published in 1992"
TL;DR: The results indicate that lithium is not an important human teratogen and women with major affective disorders who wish to have children may continue lithium therapy, provided that adequate screening tests, including level II ultrasound and fetal echocardiography, are done.
294 citations
TL;DR: This study confirms the increased likelihood of spontaneous abortions and major birth defects when chemotherapy is used during embryogenesis, whereas such a risk is not apparent beyond the first trimester in women who received chemotherapy for their cancer.
Abstract: Background.— Cancer is the second leading cause of death of women during the reproductive years, and its occurrence in pregnancy is between 0.07% and 0.1%. Methods.— To analyze the effect of cancer on pregnancy, we compared 21 pregnancies occurring during 30 years in women who received chemotherapy for their cancer with a control group matched for maternal age and composed of women not exposed to known teratogens or reproductive risks during pregnancy. Results.— Of 13 women exposed to chemotherapy during the first trimester, two of five whose pregnancies continued to term had major malformations in their infants, four had spontaneous abortions, and four had therapeutic abortions. Of four women with second-trimester exposure to chemotherapy, two had normal live births, one had a stillbirth, and one had a therapeutic abortion. All four pregnancies exposed to chemotherapy during the third trimester resulted in healthy live births. Infants exposed to chemotherapy had statistically significantly lower birth weights than their matched controls (2227±558 g vs 3519±272 g,P Conclusions.— This study confirms the increased likelihood of spontaneous abortions and major birth defects when chemotherapy is used during embryogenesis, whereas such a risk is not apparent beyond the first trimester. Because of the higher risk of stillbirth and intrauterine growth retardation, women with cancer should be monitored closely by a high-risk obstetric unit to define the optimal time of delivery. (Arch Intern Med.1992;152:573-576)
273 citations
TL;DR: The data suggest that pregnant women are at a higher risk of presenting with advanced disease because pregnancy impedes early cancer detection.
188 citations
TL;DR: Pregnant women with Hodgkin's Disease had similar distribution of stages to the controls and their outcome with non-pregnant matched women who were of similar stage of disease, age at diagnosis, and calenderic year of treatment was not different.
Abstract: The peak incidence of Hodgkin's disease occurs during the reproductive age, and its association with pregnancy is at a rate of between 1:1,000-1:6,000. We studied the effects of Hodgkin's Disease on the course and survival of 48 women who had Hodgkin's Disease and who were pregnant, and compared their outcome with non-pregnant matched women who were of similar stage of disease, age at diagnosis, and calenderic year of treatment. Twenty-year survival of pregnant women with Hodgkin's Disease was not different from that of their matched controls. Pregnant women with Hodgkin's Disease had similar distribution of stages to the controls.
140 citations
TL;DR: Both the decline in height percentile and the bony changes observed in well-chelated patients are directly related to deferoxamines therapy, implicating deferoxamine therapy as the cause of growth failure.
Abstract: We reviewed the linear growth and growth plate morphology in all children with homozygous beta thalassemia followed in Toronto, for whom monthly height percentiles were available before, and for a 36-month period after, the initiation of nightly subcutaneous deferoxamine therapy. All patients were less than 7 years of age when begun on deferoxamine, and had received nightly deferoxamine for a minimum of 36 months. Marked abnormalities of the metaphyseal growth plate were readily observed in the distal ulnar, radial, and tibial metaphyses in 11 of 37 patients in whom a significant decline in mean height percentile was also noted. (In 10 of these 11 patients, height was less than the 15th percentile after 36 months.) These 11 patients had received a significantly greater (p less than 0.025) initial and average daily dose of deferoxamine, and had maintained a significantly lower (p less than 0.025) mean serum ferritin concentration over the 36 months, than the remainder of the cohort. To determine whether deferoxamine played a causative role in growth failure, growth in patients who began deferoxamine before the age 2 years was compared to that of patients who began after age 5 years, for the period between 2 and 5 years of age. Only patients begun on deferoxamine prior to age 2 years demonstrated a significant (p less than 0.01) decline in height percentile by the third year, implicating deferoxamine therapy as the cause of growth failure. We conclude that both the decline in height percentile and the bony changes observed in well-chelated patients are directly related to deferoxamine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
133 citations
TL;DR: Both groups demonstrated a similar degree of mild to moderate respiratory depression postoperatively, which was assessed with continuous respiratory inductance plethysmography and sequential arterial blood gas analysis.
Abstract: Although epidural opioids frequently are used to provide postoperative analgesia, several articles have suggested that the analgesia after epidural fentanyl is similar to that after an equal dose of fentanyl given intravenously. To address this issue further, 29 postthoracotomy patients were studied in a randomized, double-blinded trial comparing a lumbar epidural fentanyl infusion with an intravenous fentanyl infusion for analgesia, plasma fentanyl pharmacokinetics, and respiratory effects for 20 h postoperatively. In all patients in both groups, good analgesia was achieved (pain score less than 3, maximum 10) over a similar time course, although the patients receiving epidural infusion required a significantly larger fentanyl infusion dose than did the patients receiving intravenous infusion (group receiving epidural fentanyl infusion: 1.95 +/- 0.45 micrograms.kg-1.h-1; group receiving intravenous fentanyl infusion: 1.56 +/- 0.36 micrograms.kg-1.h-1; P = 0.0002). The time course for the plasma fentanyl concentrations was similar in the two groups, and plasma fentanyl concentrations were not significantly different at any sampling period (T7-T20; group receiving epidural fentanyl infusion: 1.8 +/- 0.5 ng/ml; group receiving intravenous fentanyl infusion: 1.6 +/- 0.6 ng/ml; P = 0.06). Similarly, calculated clearance values for the two groups were not significantly different (group receiving epidural fentanyl infusion: 0.95 +/- 0.26 l.kg-1.h-1; group receiving intravenous fentanyl infusion: 0.87 +/- 0.25 l.kg-1.h-1; P = 0.3). Both groups demonstrated a similar degree of mild to moderate respiratory depression postoperatively, which was assessed with continuous respiratory inductance plethysmography and sequential arterial blood gas analysis. Side effects (nausea, vomiting, pruritus) were mild and did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
126 citations
TL;DR: Reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia appears warranted.
120 citations
TL;DR: It is document that pyrolysis of crack results in hair accumulation of cocaine, but not its benzoylecgonine metabolite, whereas after admitted cocaine use both species are detectable in hair.
Abstract: Cocaine has been shown to accumulate in hair of admitted users. Before using this test to verify cocaine use, however, it is crucial to differentiate between systemic exposure and external contamination from being in contact with crack smoke. In the present studies, the authors document that pyrolysis of crack results in hair accumulation of cocaine, but not its benzoylecgonine metabolite, whereas after admitted cocaine use both species are detectable in hair. External contamination with crack smoke is washable, whereas systemic exposure is not. The authors suggest these two criteria to distinguish systemic exposure from external contamination.
95 citations
TL;DR: The administration of prostaglandin E1 to neonates can cause gastric-outlet obstruction due to antral hyperplasia, and neonates who receive prostaglandsin E 1 at recommended doses for more than 120 hours should be closely monitored for evidence of antralhyperplasia.
Abstract: Background. An infusion of prostaglandin E1 is widely used to maintain patency of the ductus arteriosus in neonates with congenital heart disease. After gastric-outlet obstruction was recognized in several infants who received prostaglandin E1, we studied the association between the drug and this complication. Methods. We evaluated all neonates who received prostaglandin E1, in our hospital between October 1, 1989, and September 30, 1991, for clinical, radiologic, or pathological evidence of acute gastric-outlet obstruction. Results. Of the 74 neonates evaluated, 65 had no signs of gastric obstruction and were considered normal; 5 had clinical and radiologic or pathological evidence of gastric obstruction consistent with the presence of antral mucosal hyperplasia. The remaining four neonates had clinical signs of gastric obstruction, but no radiologic or pathological examinations were performed. The 5 neonates with antral hyperplasia had received prostaglandin E1 for longer periods (mean [±SD] du...
83 citations
TL;DR: In this article, the authors reviewed available data on the disposition of cancer chemotherapy in patients with hepatic dysfunction, and derived at dose recommendation, and found that prospective ascertainment of clinical indices such as hepatic enzymes and bilirubin was successful in preventing doxorubicininduced hepatotoxicity.
Abstract: OBJECTIVE:To critically review available data on the disposition of cancer chemotherapy in patients with hepatic dysfunction, and to derive at dose recommendation.DATA SOURCES:All published studies in English.STUDY SELECTION:Both human and animal studies.DATA SYNTHESIS:The available studies were sequentially qualitatively described and critically discussed.CONCLUSIONS:The liver is responsible for the metabolism and elimination of many anticancer agents. Their accumulation during hepatic insufficiency may expose the patient to increased risk of drug toxicity. A variety of clinical methods have been described to estimate the need to decrease doxorubicin dose according to degree of hepatic failure to avoid serious toxicity. In some studies prospective ascertainment of clinical indices such as hepatic enzymes and bilirubin was successful in preventing doxorubicininduced hepatotoxicity. Liver dysfunction has a major impact on cyclophosphamide pharmacokinetics. However, because such impairment leads to less pro...
74 citations
TL;DR: Although much more experience is needed, as a result of this study and other similar reports, Motherisk now offers women treated with CBZ diagnostic tests to detect neural tube defects during the second trimester of pregnancy.
TL;DR: Saliva sampling for therapeutic monitoring of ethosuximide, primidone and digoxin in infants and children, and of theophylline and caffeine in the neonate is promising, but little pediatric experience is available as yet.
Abstract: Studies suggest that saliva could be used instead of blood in the therapeutic monitoring of many drugs. This has distinct advantages in pediatrics and neonatology as saliva sampling is painless and spares blood. Stimulation of saliva secretion with a chemical stimulus (i.e. citric acid applied over the tongue) facilitates the study of younger patients. Secretory and reabsorptive processes which take place in the ductal system of the salivary glands, and the rate of flow of the secretion play major roles in the determination of the concentration of solutes in saliva. Drug passage into saliva follows the general principles of movement of drugs across biologic membranes. Only the unbound fraction of the drug in plasma is available for diffusion into saliva and a relationship exists between saliva pH and the saliva/plasma concentration ratio of many polar drugs (tolbutamide, propranolol, procainamide, etc.). However, deviations from the pH theory exist and the inter -and intra-individual variations in saliva/plasma concentration ratios of salicylate and procainamide cannot be explained solely on the basis of fluctuations of salivary pH; on the other hand, a useful relationship exists between plasma and saliva phenobarbital concentrations with no need to correct for saliva pH. The use of stimulated saliva has several advantages over resting saliva: a larger volume of the sample is obtained, the pH gradient between plasma and saliva is smaller, the variability in saliva/plasma concentration ratios of some drugs is narrowed, and less specimens are too viscous or discolored to allow drug analysis. Thorough rinsing of the mouth is required prior to saliva sampling as remnants of orally administered medicines may contaminate saliva specimens and give spuriously high values. Deviation from a simple but strict methodology accounts for some of the discrepancies found in the literature. Studies in children uniformly recommend saliva for therapeutic monitoring of phenytoin, carbamazepine and phenobarbital. Saliva sampling for therapeutic monitoring of ethosuximide, primidone and digoxin in infants and children, and of theophylline and caffeine in the neonate is promising, but little pediatric experience is available as yet. The value of saliva in therapeutic monitoring of theophylline in children is still controversial. Little of highly polar compounds such as aminoglycosides, and of polar highly protein bound drugs such as valproic acid is present in saliva. More data are still needed on the excretion of drugs in saliva in infants and in acutely ill children, and few data exist in the premature and full-term neonate.
TL;DR: Results point to a luminal localization of this secretory system for renal digoxin secretion, and digoxin did not compete with [3H]azidopine for binding in rat brush-border membranes or membranes prepared from the multidrug-resistant cell line CHRC5.
Abstract: We studied the in vivo luminal and contraluminal uptake of [3H]digoxin in dog kidney using the single-pass multiple indicator dilution method. A bolus tracer of 125I-albumin (plasma reference), creatinine, or L-[14C]glucose [extracellular reference (ecf)] and [3H]digoxin (or [3H]ouabain) was injected into the left renal artery, and timed serial samples were collected from the left renal vein (basolateral uptake) and left and right ureters (luminal uptake). [3H]ouabain was excreted solely by filtration and exhibited saturable and irreversible binding at the basolateral surface. Uptake of [3H]digoxin across the basolateral membrane was large and nonsaturable. Despite urine flow-dependent reabsorption and approximately 20% protein binding, the urine recovery ratio for [3H]-digoxin/glomerular (ecf) marker was 0.97 +/- 0.04 (n = 29), indicating net digoxin secretion. After intravenous infusions of cyclosporin in Cremophor EL (0.5-3.5 microM), the urine recovery ratio decreased in a dose-dependent manner from control values of 1.13 +/- 0.06 (n = 12) to 0.62 +/- 0.03 (n = 14). There was no change in the relative renal vein recovery. Left renal artery infusion of quinidine (37.5 micrograms.min-1.kg-1) decreased the relative urine recovery of [3H]digoxin by 46% (n = 6) but had no effect on postglomerular extraction. Cyclosporin and quinidine are known inhibitors of P-glycoprotein. But digoxin did not compete with [3H]azidopine for binding in rat brush-border membranes or membranes prepared from the multidrug-resistant cell line CHRC5. The exact mechanism for renal digoxin secretion remains to be determined, but our results point to a luminal localization of this secretory system.
TL;DR: It is concluded that, although R SCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis.
Abstract: The effect of oxygen therapy on the number of irreversibly (ISC) and reversibly (RSC) sickled cells was studied in patients with sickle cell anemia. Inhalation of 50% oxygen in patients who were not in crisis produced a significant fall in RSCs and a lesser fall in ISCs. Twenty-five subjects in sickle cell crisis were chosen at random to receive either oxygen (15 patients) or air (10 patients). Those who received oxygen showed a significant reduction in RSCs, but not in ISCs. No significant change in RSCs or ISCs occurred in the group who received air. Despite the reduction in RSCs in the oxygen-treated group, there was no significant difference between the air and oxygen groups in the duration of severe pain, opioid administration, and hospitalization. It was also observed that crisis was associated with arterial desaturation and a reduction in the number of RSCs. We conclude that, although RSCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis.
TL;DR: The data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the clinically used doses.
TL;DR: Effective analgesia was achieved during labour and a total of 1025 μg of fentanyl was infused over 11 hr 55 min until delivery of a vigorous infant with Apgar scores of 9 after one and five min, and Respiratory depression or undue sedation were not observed in the mother either during labour or in the post-partum period.
Abstract: The use of intravenous (iv) patient-controlled fentanyl analgesia during labour in a parturient with unexplained thrombocytopenia (70 × 103 · ml−1) is described. The patient self-administered boluses of 25 μg of fentanyl with a lock-out interval often min. In addition, a concurrent fentanyl infusion of 25 μg · hr−1 was given. Effective analgesia was achieved during labour and a total of 1025 μg of fentanyl was infused over 11 hr 55 min until delivery of a vigorous infant with Apgar scores of 9 after one and five min. Respiratory depression or undue sedation were not observed in the mother either during labour or in the post-partum period. At birth, maternal total plasma fentanyl concentration was 1.11 ng · ml−1, whereas neonatal umbilical total plasma fentanyl concentration was 0.43 ng · ml−1. Newborn plasma protein binding of fentanyl was lower compared to the mother (63% vs 89%). Thus, free fentanyl concentrations (0.16 ng · ml−1) were identical in the mother and newborn at delivery.
Journal Article•
TL;DR: It is concluded that outcome of pregnancy of social cocaine users and subsequent infant physical and cognitive development are within normal limits at 1.6 years of age.
Abstract: To determine the effect of first trimester cocaine use on pregnancy outcome we conducted a prospective cohort study of 30 women admitting to social cocaine use (SCU) during early pregnancy, 20 users of cannabis during the first trimester and 30 matched recreational drug-free control subjects The groups were of similar age, marital status, and obstetric history and were predominantly white They were of similar socioeconomic status (SES), however the spouses of the cocaine users were of significantly lower SES than those of both control groups (p less than 0005) The number of years of education of the cocaine users and the fathers of the SCU-exposed fetuses was significantly lower than that of the recreational drug-free control subjects (p = 0004), however, female IQ was similar among the three groups (1091 +/- 124 cocaine; 1091 +/- 252 cannabis; 1141 +/- 117 drug-free) Alcohol and cigarette use was greater among the cocaine users than among subjects of the recreational drug-free control group (p less than 0025) Cocaine and the associated lifestyle were not associated with any adverse obstetric or neonatal endpoint (pregnancy weight gain, incidence of delivery complications, gestational age, birth weight, Apgar scores, and rates of major and minor malformations) There were no differences between groups in attaining developmental milestones Mental and motor scores on the Bayley Scales of Infant Development and Vineland Adaptive Behavior Scales were identical among the three groups, studied at a mean of 197 months of age We conclude that outcome of pregnancy of social cocaine users and subsequent infant physical and cognitive development are within normal limits at 16 years of age
TL;DR: Careful follow-up of renal function should take place in children receiving iphosphamide, with special attention paid to children younger than 5 years of age and those who have receivedcis-platinum.
Abstract: The nephrotoxic potential of iphosphamide was evaluated in a retrospective analysis of all children receiving the drug at The Hospital for Sick Children in Toronto. The 25 children exhibiting nephrotoxicity did not receive more cycles or higher doses per square metre than the 78 with normal renal function. Similarly, the two groups received comparable doses and number of cycles of sodium 2-mercaptoethanesulphonate, and had similar rates of exposure to nephrotoxic drugs (except forcis-platinum). Children exhibiting nephrotoxicity were significantly younger (78.1±64.1 months) than those having normal kidney function (103.8±66.6 months) (P<0.05). Children exhibiting nephrotoxicity were more likely to have receivedcis-platinum prior to the iphosphamide (10/25, 40%) than those with normal renal function (14/73, 18%) (P<0.05). Nephrotoxicity was associated with a significant effect on growth. Careful follow-up of renal function should take place in children receiving iphosphamide, with special attention paid to children younger than 5 years of age and those who have receivedcis-platinum.
TL;DR: Treatment for cancer during adolescence carries a substantial risk for early menopause among women still menstruating at age 2 1.
TL;DR: Hair tests for assessment of fetal exposure to cocaine and cigarette smoking suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the regularly used doses.
Abstract: We describe hair tests for assessment of fetal exposure to cocaine and cigarette smoking. Cocaine and its major metabolites are incorporated into hair during the growth of the shaft and stay there for the whole life of the hair. Cocaine crosses the placenta and its metabolite benzoylecgonine, has been found in neonatal urine, meconium and hair. In order to utilize hair measurements of cocaine as a biological marker of systemic exposure, we conducted both animal and human investigations on the dose response characteristics of this phenomenon. Our data suggest that both maternal and fetal accumulation of cocaine and its metabolite follow a linear pattern within the regularly used doses. Similarly, a good correlation was observed in animals between maternal dose and fetal hair accumulation. To date, no biological markers have been identified that can predict the extent of fetal exposure to the adverse effects of toxic constituents of cigarette smoke. We measured maternal and fetal hair concentrations of nicotine and cotinine in mother-infant pairs. Smoking mothers had a mean of 21.3 +/- 18 ng/mg hair nicotine and 6 +/- 9.2 ng/mg of cotinine, significantly more than nonsmokers (0.9 +/- 0.8 ng/mg nicotine and 0.3 +/- 0.5 ng/mg cotinine, p < 0.0001). Babies of smokers had a mean nicotine concentration of 6 +/- 9.2 ng/mg (range 0-27.3) and cotinine of 2.1 +/- 3.7 ng/mg (range 0-12.2), significantly more than babies of nonsmokers (nicotine 0.6 +/- 0.7 ng/mg and cotinine 0.2 +/- 0.5 ng/mg; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: It is concluded that E MLA patch and cream have a similar efficacy in children undergoing venipuncture and young children recently diagnosed with chronic disease are most likely to benefit from EMLA.
Abstract: The emulsion of lidocaine and prilocaine (EMLA) is effective in preventing the pain of venipuncture in children. It is therefore important to identify children who could benefit the most from EMLA. We studied the safety and feasibility of two methods of application of EMLA (patch and cream) in a randomized, open-label trial of EMLA patch versus EMLA cream in 160 children with chronic diseases undergoing venipuncture. EMLA patch or cream was applied 60 to 120 min before puncture. Pain was assessed by the children using a visual analogue score. Children also scored the pain of their last puncture and the pain of removing the tape. EMLA patch and cream had similar efficacy (visual analogue scores for the venipuncture were 8.5 ± 16 and 9.5 ± 17 out of 100, respectively). Side effects occurred in similar frequencies in the two groups. Adhesiveness of the patch was less effective than that of the cream with Tegaderm. Age was a major determinant of pain perception; younger children recalled more severe pain in their previous puncture. Children recently diagnosed had higher visual analogue scores than those with a long history of chronic disease. We concluded that EMLA patch and cream have a similar efficacy in children undergoing venipuncture. Young children recently diagnosed with chronic disease are most likely to benefit from EMLA.
TL;DR: Because it is a weak organic acid, the tubular secretion of methotrexate depends on urinary pH, and at night urinary pH is more acidic, this may result in more reabsorption and hence reduced renal clearance.
Abstract: Survival has been shown to improve when maintenance therapy for acute lymphocytic leukemia in children is given at night rather during the day. We examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In a crossover study, we determined the pharmacokinetics of intravenous methotrexate at 10:00 and 21:00 h in six children with standard or high-risk leukemia. During the study, children refrained from concomitant drugs (6-mercaptopurine and trimethoprim sulfamethoxazole). There was a significant fall in methotrexate plasma clearance at night (from 5.6 ± 3 ml/min/kg to 4.7 ± 2.3 ml/min/kg p > 0.05). Renal clearance of methotrexate tended to decrease at night and unbound renal clearance decreased significantly (from 17.5 ± 1.7 ml/min/kg to 8.5 ± 3.6 ml/min/kg p > 0.05). Creatinine clearance did not exhibit diurnal variation, when comparing two 12-h collections, but there was a significant decrease in the nonglomerular clearance of methotrexate (fro...
TL;DR: To quantify the perception of teratogenic risk of cocaine by the public, physicians, and by pregnant women who were counseled following gestational exposure to the drug, a visual analogue scale was used to quantify the tendency to terminate/continue the pregnancy after first trimester exposure.
Abstract: While there has been a substantial increase in recreational use of cocaine by young adults, conclusive evidence for cocaine teratogenicity in humans is lacking, and even those believing the drug is teratogenic agree that the rates are quite small. While counseling pregnant women on their teratogenic risk, it was our impression that there is an unrealistically high perception of reproductive risk of cocaine. We wished to quantify the perception of teratogenic risk of cocaine by the public, physicians, and by pregnant women who were counseled following gestational exposure to the drug. Women taking cocaine during the first trimester of pregnancy (n = 54), controls with post secondary education (n = 30), and physicians (n = 30) were asked, using a visual analogue scale, to quantify the teratogenic risk of cocaine and the tendency to terminate/continue the pregnancy after first trimester exposure; in the case of the "public" and physicians this was a hypothetical question. Both physicians and the controls perceived cocaine to be teratogenic (13.4 +/- 11% risk of major malformations by physicians, and 56.5 +/- 22.8% by the "public"). The controls believed cocaine to be as hazardous as thalidomide (57.2 +/- 25.6% risk for thalidomide). Asked whether they would wish to terminate such pregnancy in their family, most physicians (56%) and the controls (70%) had a greater than 50% tendency to terminate.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The results confirm the marked increase in breast cancer risk among women with atypical hyperplasia, particularly in premenopausal women and suggest that these women should be encouraged to undergo frequent breast cancer screening.
TL;DR: Clinical Pharmacology and Therapeutics (1992) 52, 102–103; doi:10.1038/clpt.1992.108
Abstract: Clinical Pharmacology and Therapeutics (1992) 52, 102–103; doi:10.1038/clpt.1992.108
TL;DR: To separate the effects of transplantation and cyclosporine on digoxin pharmacokinetics, pharmacokinetic studies were performed in dogs to allow controlled experimental conditions for evaluation of the digoxin‐cyclosporines interaction.
Abstract: Most patients needing cardiac transplantation are treated with digoxin for heart failure Because of its narrow therapeutic range, even recommended doses of digoxin may cause severe toxicity Several drugs, including quinidine, amiodarone, verapamil, and propafenone can interact with digoxin, leading to toxic accumulation of the glycoside The authors have recently reported two cases of severe digitalis toxicity after the initiation of cyclosporine treatment in patients awaiting cardiac transplantation A preliminary study on two additional patients suggested that cyclosporine reduced the plasma clearance and volume of distribution of digoxin To assess the mechanism of this interaction, the authors studied digoxin pharmacokinetics in patients awaiting cardiac transplantation and again after the surgery, during chronic cyclosporine therapy To separate the effects of transplantation and cyclosporine on digoxin pharmacokinetics, pharmacokinetic studies were subsequently performed in dogs to allow controlled experimental conditions for evaluation of the digoxin-cyclosporine interaction
TL;DR: If you continue on lithium during pregnancy, you will need close monitoring of your blood lithium levels and it is best to take the lowest dose that works for you and spread the dose out over the course of the day.