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Biomedical subjects

W A Colburn

Publications and source records attributed to W A Colburn.

At least 109 records · Page 6Linked to original sources
PubMed1978

Interaction of chloramphenicol with phenytoin and phenobarbital. Case report.

The effect of chloramphenicol therapy (48 mg/kg/day) on the serum concentrations of phenytoin and phenobarbital was studied in a patient previously stabilized on anticonvulsant medications. Phenytoin, 12 mg/kg/day, and phenobarbital, 5 mg/kg/day resulted in serum concentrations averaging 10.8 microgram/ml before and 30.5 microgram/ml, after chloramphenicol therapy. A reduction in dose of both phenytoin and phenobarbital was required to minimize adverse effects during the course of chloramphenicol therapy. An average daily dose of phenytoin of 9.1 mg/kg resulted in an average serum concentration of 17.8 microgram/ml. A daily dose of phenobarbital of 4.0 mg/kg resulted in an average serum concentration of 37.1 microgram/ml. These changes indicate 50.5% and 40.4% decreases in clearance of phenytoin and phenobarbital. Multiple-dose nonlinear regression analysis of phenytoin and phenobarbital serum concentration data obtained during chloramphenicol therapy indicated a 62.5% and a 29.5% decrease in clearance. Subsequent serum concentration monitoring demonstrated a similar reduction in phenobarbital clearance when chloramphenicol was added to phenobarbital alone.

Adult↗
PubMed1978

Absorption kinetics of hydroflumethiazide.

The pharmacokinetics of hydroflumethiazide after oral administration of a 100-mg dose to 12 volunteers were evaluated to determine whether absorption of the drug is best described by zero-order or first-order absorption. Comparison of the two absorption models was based on three criteria: (1) correlation coefficients; (2) standard deviations of the parameter estimates; and (3) visual fits. Evaluation of the individual results in light of each criterion showed that the zero-order absorption model is the more appropriate one for describing the hydroflumethiazide data.

Administration, Oral↗
PubMed1978

Use of MULTDOS for pharmacokinetic analysis of ethosuximide data during repetitive administration of single or divided daily doses.

MULTDOS, a computer method to curve fit data obtained on multiple dosing, was used with either the 1969 or 1974 version of the NONLIN program to compare the pharmacokinetic parameters of ethosuximide during repetitive administration of single or divided daily doses. Elimination rate constants, excretion rate constants, and apparent volumes of distribution were similar between the two dosing regimens and essentially identical between the two nonlinear regression programs.

Computers↗
PubMed1977

Pharmacokinetic analysis of drug concentration data obtained during repetitive drug administration.

A digital computer curve-fitting method, designed to estimate pharmacokinetic model constants by utilizing all drug concentration-time data collected during repetitive dosing studies, was applied to data manifesting systematic dose-to-dose variability in one or another of the pharmacokinetic parameters. The method accurately determined dose-to-dose changes in absorption or elimination rate constants or in the apparent volume of distribution, and it would be useful for detecting phenomena such as self-induction and self-inhibition that may occur during multiple-dose administration. The method can also be used to analyze multiple-dose data of drugs exhibiting capacity-limited elimination and to obtain estimates of the Michaelis-Menten parameters.

Computers↗
PubMed1977

Pharmacokinetics of erythromycin on repetitive dosing.

Serum erythromycin concentration data from several repetitive dosing studies were analyzed with newly developed computer methods for fitting multiple-dose data and generating nonlinear least-squares estimates of pharmacokinetic parameters. This analysis indicates that the pharmacokinetics of erythromycin can be described by a one-compartment linear model with the following characteristics: (a) a lag time between the time of drug administration and the onset of absorption; (b) apparent zero-order rather than first-order absorption; (c) dose-to-dose variability in the rate and extent of absorption; and (d) day-to-day variability in the kinetics of elimination. The bioavailability of the third dose of erythromycin on a given day is considerably lower than that of the second dose or of the fourth and last dose of the day. The average apparent half-life of erythromycin was 1.8 hour on day 1 and 2.6 hours on day 3 of the repetitive dosing regimen.

Adult↗
PubMed1977

Plasma protein binding and metabolic clearance of phenytoin in the rat.

The purpose [corrected] of this investigation was to determine the effects of certain changes in plasma protein binding on the disposition of phenytoin after i.v. administration in the rat. Treatment of rats with sulfisoxazole and oleic acid significantly reduced plasma protein binding of phenytoin. The displacement of phenytoin from plasma proteins by sulfisoxazole had no significant effect on the elimination of phenytoin whereas comparable displacement by oleic acid produced an increase in the apparent volume of distribution and a marked decrease in the metabolic clearance of the drug. A similar difference in metabolic clearance was noted when phenytoin elimination was determined as a function of the intrinsic ability of the rat to bind phenytoin in the plasma. Rats showing relatively high plasma protein binding of phenytoin cleared the drug much more rapidly than rats showing relatively low plasma protein binding of phenytoin. Assuming that an endogenous inhibitor is responsible for both the decreased plasma protein binding and decreased metabllic clearance of phenytoin in rats with an intrinsically reduced ability to bind phenytoin in plasma, this inhibitor is evidently similar to oleic acid in its effects.

Animals↗
PubMed1976

Comparative serum prednisone and prednisolone concentrations following prednisone or prednisolone administration to beagle dogs.

The relative serum prednisone and prednisolone concentrations were determined following the administration of prednisone or prednisolone as 5-mg tablets to male beagle dogs. Serum prednisone concentrations were significantly greater following prednisone administration than they were following prednisolone administration. Serum prednisolone concentrations were significantly greater following treatment with prednisolone than with prednisone. The combined prednisone and prednisolone areas under the serum concentration-time curves were similar for the two treatments.

Animals↗
PubMed1976

Pharmacokinetic model for serum concentrations of ampicillin in the newborn infant.

The time course of ampicillin concentrations in the sera of three newborn infants during and upon termination of intravenous infusion at a constant rate can be described by a two-compartment pharmacokinetic model. The parameters of the model were determined by simultaneously fitting the serum concentration data obtained during and after the infusion by means of a nonlinear regression program with the aid of a digital computer. The half-life of ampicillin in the infants ranged from 2.1 to 2.9 hr; these values are more than twice those observed in adults with normal renal function.

Ampicillin↗
PubMed1975

Radioimmunoassay for fluoxymesterone (Halotestin).

A specific, sensitive, precise and accurate radioimmunoassay has been developed for fluoxymesterone, 9alpha-fluoro-11beta,17beta-dihydroxy-17-methyl-4-androsten-3-one (Halotestin). The method is capable of detecting 25 picograms of drug in 0.1 ml of unextracted serum. The primary antibody was prepared against fluoxymesterone 3-(0-(carboxy-methoxime)) (CMO) bovine serum albumin. The specificity of the assay is greatly influenced by the hydroxyl group at position 11 and the methyl group at position 17. Physiological levels of endogenous steroids did not cross-react significantly with the primary antibody. Blood levels of fluoxymesterone were determined in both human subjects and male beagle dogs after oral administration of Halotestin.

Animals↗