The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

Clinical applications of fast liquid chromatography: a review on the analysis of cardiovascular drugs and their metabolites.

http://prr.hec.gov.pk/jspui/bitstream/123456789/7791/1/Mudassar%20Ashraf%20Final%20Full%20Thesis.pdf

Pharmacokinetics and Bioequivalence of Cefixime in Healthy Male and Female Volunteers

Enalapril is a prodrug that is metabolized to its main active metabolite, enalaprilat that is a potent inhibitor of angiotensin converting enzyme (ACE). A simple, rapid, sensitive, precise and accurate SIM GC–MS method, using solid-phase extraction and derivatization with methyl iodide, for the quantitative determination of enalapril and enalaprilat in human plasma was developed and validated. The ions at m/z 220 for enalapril, m/z 234 for enalaprilat and m/z 172 for internal standard, perindopril, were monitored. The calibration graphs for the analytes were linear in the 5–160 ng mL−1 concentration range (r > 0.999). Intra-day and inter-day precision for enalapril ranged from 2.4 to 3.5 and 3.9 to 7.9%, and for enalaprilat from 5.3 to 7.8 and 6.7 to 9.1%. Accuracy was better than 105.5% for both enalapril and enalaprilat. The method was sensitive with a lower limit of quantitation (LLOQ) of 2 ng mL−1 for both analytes and was not interfered by other plasma components. The method was applied for the determination of enalaprilat in a pharmacokinetic study after single oral administration of 20 mg enalapril to 24 healthy subjects.

GC–MS Simultaneous Determination of Enalapril and Enalaprilat in Human Plasma: Application to a Clinical Pharmacokinetic Study

Enalapril maleate, available on the market in a variety of different pharmaceutical formulations, is commonly used for the control of systemic arterial hypertension. Many therapeutical failures have been reported thus far in clinical practice with respect to switching between different pharmaceutical formulations of the same product during pharmacological therapy. In the present study, plasma concentrations of enalapril and enalaprilate were measured in hypertensive patients undergoing treatment with different pharmaceutical formulations. Materials and methods: Pharmaceutical formulations studied included the reference brand product, a generic formulation, and a third drug product marketed as “similar”; plasma samples were obtained from 30 hypertensive volunteer patients. Drug was extracted from the plasma by solid phase extraction and determined by liquid chromatography-tandem mass spectrometry. The method was validated for the main analytical parameters. Results: The analytical method developed in this study, using liquid chromatography-tandem mass spectrometry, was confirmed as suitable for application in the determination of plasma concentrations in patients and subsequently revealed statistically significant differences in plasma concentrations between the 3 treatment groups. Conclusions: Such differences reinforce the hypothesis that the bioequivalence tests currently proposed by the regulatory authorities to promote interchangeability between pharmaceutical formulations may not in fact represent a definitive parameter for guaranteeing similar plasma concentrations.

A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using solid phase extraction for the simultaneous determination of plasma concentrations of enalapril and enalaprilate in hypertensive patients treated with different pharmaceutical formulations.

The pharmacokinetics parameters and relative bioavailability studies of generic formulation enalapril tablets (Anapril® 20), the test product manufactured by Birzeit Pharmaceutical Company (Birzeit, Palestine) compared to the reference product Vasotec® tablets (Merck Sharpe Dohme, USA) were conducted in 18 healthy male volunteers following a single dose, two‐period, crossover design Each volunteer received 20 mg enalapril tablets of both formulations with a one week washout period Plasma collected over a period of 24 hours after administration were analyzed for the active metabolite enalaprilat by high performance liquid chromatography (HPLC) Pharmacokinetic parameters were determined by using non‐compartmental analysis The results indicated that Cmax 4644 and 4517 ng/mL, Tmax of 20 and 15 hr, AUC(0–24) of 24406 and 23741 ng · mL/hr, AUC(0–∞)) were 29471 and 28221 ng · hr/mL and MRT were 474 and 470 hr, t1/2 495 and 50 hr, in test and reference products, respectively The relative

Pharmacokinetic Parameters and Relative Bioavailability of Two Tablet Formulations of Enalapril Maleate

A simple and reliable isocratic reversed phase high performance liquid chromatography (HPLC) method for the determination of enalaprilat in human plasma is described. After plasma extraction, enalaprilat is analyzed using a µ Bondapak C18 column kept at 50°C. The mobile phase consists of 60% A (0.01 M KH2PO4, pH 4.0) and 40% B (80% of 50:50 CH3CN:CH3OH + 20% A) v/v. Enalaprilat is monitored by UV detection at 205 nm. The method is quite simple and sufficiently sensitive, with a limit of quantitation of 5 ng/mL and limit of detection of 1 ng/mL; within day and between‐days assays showed a relative standard deviation (RSD) below 15%.

Simple HPLC Method for the Determination of Enalaprilat in Human Plasma

This investigation was carried out to evaluate the bioavailability of the generic product of digoxin 0.25 mg (cardixin) relative to a reference product, lanoxin (0.25 mg) tablets. The two formulations were found to be similar in in vitro assay (dissolution) as stipulated by USP XXIII. The comparison is carried out on 12 healthy male volunteers, who received a single dose (0.25 mg) of cardixin (product A) lanoxin (product B) as a reference product orally in the fasting state, in a randomized balanced two‐way crossover design. After dosing, serial blood samples were collected for a period of 12 hr. Plasma samples were analyzed for digoxin by a sensitive and validated enzyme immunoassay method (ELISA). The maximum plasma concentration curve, up to the last measurable concentration (AUC0–24), was analyzed under the assumption of a multiplicative model. The time to maximum concentration (T max) was analyzed, assuming an additive model. The parametric confidence intervals (90%) of the mean values of th...

Comparative bioavailability study of two tablet formulations of digoxin.

Asthma is a public health problem for developed countries. It attacks all age groups but often starts in childhood. Theophylline ethanoate of piperazine in a suppository form is one of the treatments of asthmatic children. The pharmacokinetics of theophylline were evaluated in 24 healthy male subjects after administration of theophylline ethanoate of piperazine suppositories (PR) (Minophylline 500 mg. Alexandria Co.) and single injection intravenous (IV) of theophylline ethanoate of piperazine (Minophylline ampoules 500 mg Alexandria Co.). The theophylline serum levels were determined by an ELISA method. Peak theophylline plasma concentration, Cmax, (mean +/- S.D) was 21.5 +/- 2.10 microg/mL & 14 +/- 0.90 microg/mL; AUC(0-t), values were 80.9 and 67. 4 microg x ml x hr for the reference IV preparation and suppositories, respectively. The median peak time, Tmax, was 0.5 hr for theophylline rectal administration. The above mentioned results demonstrate the possibilities of using theophylline (Minophylline Suppositories--500 mg Alexandria Co.) in asthmatic children in rural and desert areas away from health care personnel.

Lobna F. Wahman

Papers

Pharmacokinetic Parameters and Relative Bioavailability of Two Tablet Formulations of Enalapril Maleate

Simple HPLC Method for the Determination of Enalaprilat in Human Plasma

Comparative bioavailability study of two tablet formulations of digoxin.

Pharmacokinetics of Theophylline after Administration of Suppositories Formulation