Guide for the Care and Use of Laboratory Animals

Considerable advances have occurred in recent years in the scientific knowledge of the benefits of breastfeeding, the mechanisms underlying these benefits, and in the clinical management of breastfeeding. This policy statement on breastfeeding replaces the 1997 policy statement of the American Academy of Pediatrics and reflects this newer knowledge and the supporting publications. The benefits of breastfeeding for the infant, the mother, and the community are summarized, and recommendations to guide the pediatrician and other health care professionals in assisting mothers in the initiation and maintenance of breastfeeding for healthy term infants and high-risk infants are presented. The policy statement delineates various ways in which pediatricians can promote, protect, and support breastfeeding not only in their individual practices but also in the hospital, medical school, community, and nation.

/pdf/breastfeeding-and-the-use-of-human-milk-2m74a0njro.pdf

Breastfeeding and the Use of Human Milk

In 1940, the world of pharmacology was revolutionized by the appearance of the first edition of this now-classic text. Edited by Lou Goodman and Al Gilman, it was a joy to read and a beacon in the darkness for teachers, students, and practitioners. (I can recall physicians saying they kept it on their bedside table for their nightly reading and pleasure.) The new edition remains a competently written and authoritative book, although it is now put together by 58 people instead of two, with the inevitable problems posed by such a division of labor. (One may envy the editors and the publishers the income from this best seller, but not the task of nagging recalcitrant authors with no respect for deadlines.) One may question, however, as in recent editions, the wisdom of combining a textbook for students and a reference for physicians. Those of us who teach second-year medical students

Goodman & Gilman's The Pharmacological Basis of Therapeutics

https://cyberleninka.org/article/n/148766.pdf

Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation

Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the efficacy and toxicity of many medications. Pharmacogenomic studies are rapidly elucidating the inherited nature of these differences in drug disposition and effects, thereby enhancing drug discovery and providing a stronger scientific basis for optimizing drug therapy on the basis of each patient's genetic constitution.

https://science.sciencemag.org/content/sci/286/5439/487.full.pdf

Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics

Since its introduction 11 years ago,75, 77 the antipyrine test, devised to determine quantitatively the effect of individual environmental factors on hepatic drug‐metabolizing capacity in normal subjects, has been widely used by clinical pharmacologists, as indicated by the large number of applications listed in Table 1. Yet there have been several technical modifications, new extensions and unresolved problems, and an increasing number of apparently conflicting results. This warrants a fresh look at the antipyrine test and a critical reassessment of its applications and limitations.

The antipyrine test in clinical pharmacology: Conceptions and misconceptions

Antipyrine was administered to identical or monozygotic twins and to fraternal or dizygotic twins. Individuals with identical genotypes (monozygotic twins) exhibited significantly less variability in antipyrine halflife than did genetically different individuals (dizygotic twins). Therefore variations in antipyrine metabolism appear to be determined genetically rather than environmentally. In the 36 twins tested, antipyrine half-lives varied between 5.1 and 16.7 hours. No significant correlation occurred between half-lives for phenylbutazone and antipyrine in the 28 twins who received both drugs.

http://science.sciencemag.org/content/sci/161/3836/72.full.pdf

Genetic Control of Drug Levels in Man: Antipyrine

The rate of hepatic metabolism of dimethylaminoantipyrine (aminopyrine), which occurs primarily through N-demethylation, was assessed by measurement of the specific activity of14CO2excrete...

Quantitative assessment of hepatic function by breath analysis after oral administration of (14C)aminopyrine.

To determine whether hepatic drug metabolism might be conveniently assessed by a breath analysis technic, 4-dimethyl-14C-amino-antipyrine (aminopyrine) was administered orally to healthy ambulant and nonambulant volunteers and to patients with portal cirrhosis; some of the volunteers were restudied after pretreatment with either phenobarbital or disulfiram. 14CO2 output was estimated semiquantitatively from interval breath samples. Aminopyrine metabolic clearance rate and 12-hour breath 14CO2 output in the healthy volunteers studied before and after drug pretreatment correlated highly(r = 0.91). The metabolic clearance rate was 46 ± 7 ml per minute (mean ± S.E.) in the patients with portal cirrhosis, and 122 ± 20 ml per minute in the healthy controls (p < 0.01). Twelve-hour breath 14CO2 output was 13.8 ± 1.5 per cent in the patients with portal cirrhosis, and 32.6 ± 2.3 per cent in the nonambulant controls (p < 0.01). The data suggest that in vivo breath analysis after administration of 14C-amino...

Assessment of aminopyrine metabolism in man by breath analysis after oral administration of 14C-aminopyrine. Effects of phenobarbital, disulfiram and portal cirrhosis.

Phenylbutazone was administered to seven pairs of identical (monozygotic) twins and to seven pairs of fraternal (dizygotic) twins Individual half-lives ranged from 12 to 73 days Subjects with identical genotypes (monozygotic twins) exhibited very similar phenylbutazone half-lives; significantly greater differences in half-life occurred in dizygotic twins The previously established large variations among individuals in phenylbutazone metabolism appear to be genetically, rather than environmentally, determined

Elliot S. Vesell

Papers

The antipyrine test in clinical pharmacology: Conceptions and misconceptions

Genetic Control of Drug Levels in Man: Antipyrine

Quantitative assessment of hepatic function by breath analysis after oral administration of (14C)aminopyrine.

Assessment of aminopyrine metabolism in man by breath analysis after oral administration of 14C-aminopyrine. Effects of phenobarbital, disulfiram and portal cirrhosis.

Genetic control of drug levels in man: phenylbutazone.