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Biomedical subjects

S J Yaffe

Publications and source records attributed to S J Yaffe.

At least 55 records · Page 3Linked to original sources
PubMed1980

Reproductive dysfunction in male rats following prenatal exposure to phenobarbital.

The effect of prenatal exposure to phenobarbital (40mg/Kg/day from day 12 to day 19 of pregnancy) on sexual development of male offspring was investigated. Anogenital distance of the male offspring exposed to phenobarbital was significantly smaller. Testicular descent was delayed by 1-3 days, but the age of onset of puberty did not change. Fertility was reduced significantly (P less than .05) in phenobarbital exposed animals compared to that of control. Upon sacrifice, the weight of the seminal vesicles of treated rats was smaller compared to control, but the weight of liver was increased. Hormone measurement in adult age showed a significant reduction in both testosterone and luteinizing hormone levels in the phenobarbital exposed males. Moreover, prenatal treatment with phenobarbital produced an elevated level of cytoplasmic androgen receptor in the seminal vesicles of the adult rats. These findings suggest that phenobarbital treatment during prenatal development can produce some permanent alterations in the process of sexual maturation.

Animals↗
PubMed1980

Disposition of chloramphenicol in low birth weight infants.

Although infrequently an antibiotic of first choice for neonates, chloramphenicol (CL) may be indicated in selected instances of infection caused by aminoglycoside-resistant enterobacteriaciae, anaerobes, and ampicillin-resistant Haemophilus influenzae. Use of CL in neonates has been limited since the recognition that vascular collapse may occur as a consequence of dosage regimens tolerated by adults. With an assay that detects only active CL, we studied drug disposition in 13 low birth weight infants, eight between 1 and 8 days of age (group I), and five between 11 days and 8 weeks of age (group II). Peak serum CL concentrations ranged from 11.2 to 36.2 microgram/ml in group I and from 10.0 to 36.2 microgram/ml in group II, at doses ranging from 15 to 50 mg/kg/day, and 25 to 50 mg/kg/day, in groups I and II, respectively. Serum CL half-lives (T1/2) ranged from 10 to 36 hours in four of the eight group I patients; three of the remaining patients had T1/2 greater than 48 hours and the fourth patient accumulated CL in the interval between doses. T1/2 in group II ranged from 5.5 to 15.7 hours. Observed differences in T1/2 between groups I and II were statistically significant (P = .05) and could not be accounted for by factors other than postnatal age. These preliminary data suggest that although there appears to be an inverse relationship between CL T1/2 and postnatal age, there is sufficient variability in serum levels that monitoring must be performed in low birth weight infants treated with this drug.

Chloramphenicol↗
PubMed1979

Aspirin dosage for infants and children.

The labeled dosage schedule that has long been on pediatric aspirin preparations is at variance with the recommendation in authoritative medical references, studies demonstrating antipyretic effectiveness in children, and the prescribing habits of pediatricians as revealed by a poll conducted by the authors. Aspirin pharmacokinetics are influenced by a number of physiologic factors, as well as by dosage, and complicate the problem of assuring safe and effective pediatric use. Basic pharmacokinetic considerations indicate that the increase in size of individual doses needed to assure therapeutic salicyate blood levels, thereby removing the temptation of parents to administer the drug too often, is made permissible (i.e., safe while effective) by expanding the interdose interval to four hours instead of three. A revised pediatric aspirin disage schedule is presented that better meets the practices of the pediatric community and the needs of consumers.

Age Factors↗
PubMed1979

Theophylline pharmacokinetics in the young infant.

The pharmacokinetics of theophylline were investigated in 13 infants, 4 to 18 months of age. An inverse relationship was found between theophylline half-life and age. Volume of distribution did not differ from that reported by other authors in similarly aged infants. Our data suggest that childhood clearance rates of elimination can be achieved by 6 months of age. The decreased theophylline elimination observed in the smaller infant indicates that the usual pediatric dosing recommendations cannot be used routinely. Until more specific data are available in the infant under 6 months, the authors reaffirm individualization of theophylline dosage to maintain therapeutic levels and avoid toxicity.

Age Factors↗
PubMed1978

Drugs and pregnancy.

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Abnormalities, Drug-Induced↗
PubMed1977

Pharmacokinetics of methicillin in patients with cystic fibrosis.

The disposition of methicillin in normal subjects and in subjects with cystic fibrosis (CF) was studied after administration of single intravenous doses of 15 mg/kg. The area under the serum concentration vs. time curve for CF patients was, on the average, only 75% of that found for normal subjects. The low concentrations in serum were caused by more rapid urinary excretion of the antibiotic, with rates of renal clearance averaging 425 ml/min per 1.73 m2 in the patients with CF and 362 ml/min per 1.73 m2 in the normal subjects. No differences were found in volumes of distribution and metabolic clearance rates of methicillin or in rates of creatinine clearance between the two groups of subjects. These data support previous findings with dicloxacillin which show that patients with CF exhibit unusually rapid, active tubular secretion of certain penicillins that may necessitate use of larger doses of these drugs in treatment of infections.

Adolescent↗
PubMed1977

Renal clearance of digoxin in young infants.

The renal clearance of digoxin and creatinine were measured in eleven infants, aged one to five months, with congenital heart disease and heart failure. The renal clearances of digoxin were low at one month of age (50 ml/min/1.73 m2) but increased progressively until the adult range was attained at about five months of age (130-150 ml/min/1.73 m2). At any given age, however, the renal clearance of digoxin was almost twice as great as the simultaneously determined creatinine clearance (mean ratio 1.73). This stands in marked contract to older subjects where creatinine and digoxin clearances are usually similar. These data explain (in part) the larger digoxin dosage requirement of infants.

Aging↗
PubMed1976

Tissue and erythrocyte distribution of digoxin in infants.

The distribution of digoxin in the myocardium, skeletal muscle, erythrocytes, and plasma (or serum) was studied in 19 infants. There was a linear relationship between myocardium and serum concentrations and no saturation was observed over the serum concentration range of 0.5-8.6 ng/ml. Myocardium uptake of digoxin was nearly twice as great in infants as in adults at any given serum concentration. Erythrocyte: plasma concentration ratios of digoxin were one-third smaller during digitalization than during maintenance digoxin therapy. The latter ratios were also three times greater in infants than found previously in adults. Their findings are consistent with a greater apparent volume of distribution of digoxin in infants and may partly explain the unusually large therapeutic doses needed in infants.

Digoxin↗
PubMed1976

Pharmacokinetics of gentamicin during peritoneal dialysis in children.

The pharmacokinetics of gentamicin were examined on two occasions using intravenous and intraperitoneal routes in five children undergoing intermittent peritoneal dialysis for chronic renal failure. Serum, urine and dialysis fluid (DF) were assayed microbiologically for gentamicin and the data were subjected to computer analysis using equations evolved for a two-compartment model which considered the bi-directional flux of the drug. Following i.v. injection of 1 mg/kg of gentamicin, the apparent volume of distribution averaged 23% (range, 13 to 36%) of body wt (similar to normal), the mean half-life was 21 hr (range 9 to 37 hr; normal, 2 hr) and the peritoneal clearance averaged 4.0 ml/min/m2 (range, 1.2 to 7.0 ml/min/m2). During peritoneal administration of gentamicin (15 mg/liter of DF, 0.7 liters/m2 administered in each cycle over 9 to 12 cycles), serum concentrations increased towards extrapolated steady-state levels which averaged 42% (range, 25 to 68%) of DF concentrations. The mean renal clearance of gentamicin was only 1.6 ml/min/m2 while total body clearance ranged from 2.3 to 8.0 ml/min/m2 mostly occurring by a variable degree of dialysance. Peritoneal clearances and half-lives of gentamicin were similar in each patient following either treatment mode. The appreciable variability in gentamicin pharmacokinetics among adolescent patients with renal insufficiency necessitates dosage adjustments based on measurements of serum concentrations.

Absorption↗