Notification about allergic drug reactions.
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Biomedical subjects
Publications and source records attributed to M Danish.
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The disposition of theophylline was examined in seven children with asthma on two occasions before and on one occasion after chronic phenobarbital dosing (2 mg/kg/day). There was little intrapatient variability in apparent theophylline clearance between the two baseline assessments (0.081 versus 0.073 L/hr/kg). After 19 days of phenobarbital therapy, there was a significant increase in apparent theophylline clearance (0.104 versus 0.077 L/hr/kg), accompanied by a 30% decrease in the mean steady-state serum theophylline concentration (12.0 versus 8.4 micrograms/ml). The inducing effect of phenobarbital on theophylline metabolism may require theophylline dosage adjustment in patients with asthma who receive both drugs concurrently to maintain a given average steady-state theophylline concentration.
An oral theophylline product was given to eight lean, normal subjects and eight obese subjects (four with asthma and four normals) in a single-dose study. The mean apparent volume of distribution (Vd) was 0.472 +/- 0.08 liters/kg for the lean group and 0.321 +/- 0.063 liters/kg for the obese group (P less than 0.001). When Vd wax expressed in liters, there was no difference between the two groups (lean:26.9 +/- 6.0 liters, obese: 28.5 +/- 6.3 liters). An inverse relationship existed between the ratio of total body weight to ideal body weight (TBW/IBW) and Vd expressed in liters/kg. One obese subject was studied before and after a weight loss of about 32 kg. The values of Vd in this subject were 32.1 and 34.9 liters, respectively. These data indicated that theophylline is not extensively distributed into adipose tissue and that loading-dose calculations should be based on ideal body weight. No difference in clearance of theophylline was seen between the two groups.
The pharmacokinetics of two unmatched populations of asthmatic children, one from an asthmatic convalescent center in Denver and the other from an urban outpatient clinic, are compared after single and repeated dosing of a new asthma formulation, oxtriphylline syrup. Significant differences (p less than 0.05) in populations' theophylline total body clearance, apparent volume of distribution and absorption rates suggest future studies of multiple center design representing patterns of asthma more typical to the population at large would be more appropriate for selection of theophylline dosage guidelines.
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.
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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.
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The pharmacokinetics of gentamicin, kanamycin, and creatinine were studied in patients undergoing hemodialysis. After intravenous injection of single doses of the drugs, 50 to 60% of the doses of both antibiotics were cleared from the body during a 6-h period; this occurred almost entirely by the hemodialysis process. No correlation was found between the dialysance of the aminoglycosides and creatinine. The pharmacokinetic data were used to make dosage regimen recommendations for treatment of hemodialysis patients with these antibiotics.