Effect of Enzyme Induction on Bioavailability of Hetacillin in Patients Treated with Anticonvulsants and Chlorpromazine

Overview

Journal Eur J Drug Metab Pharmacokinet

Date 1990 Jan 1

PMID 2384113

Authors

P Galanopoulou

C Karageorgiou

K Dimakopoulou

Affiliations

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Abstract

The effect of liver enzyme induction on bioavailability of hetacillin was studied in patients chronically treated with anticonvulsants or chlorpromazine. 24 chronic psychiatric patients classified according to their medication in two groups (anticonvulsants, chlorpromazine) and one group of 11 healthy volunteers, received an i.m. administration of 500 mg hetacillin. Serum levels of ampicillin derived from hetacillin in blood samples taken 2, 4 and 6 hours after the injection were measured and the half-life of the antibiotic was determined for each group. Urinary D-glucaric acid was considered the induction index. Correlation coefficients between the induction index and pharmacokinetic parameters of hetacillin were also determined. Anticonvulsants and chlorpromazine induced the liver microsomal enzymes as demonstrated by the increased D-glucaric acid excretion (P less than 0.001 - P less than 0.05). No statistically significant differences were found in serum levels and half-life of the antibiotic. Correlation coefficients suggest that enzyme induction and hetacillin bioavailability are not significantly related.

References

von Bahr C, Schenkman J, Orrenius S . Effect of phenobarbital and 3,4-benzpyrene treatment of rats on the microsomal binding and hydroxylation of nortriptyline and desmethyl-imipramine: evidence for qualitative changes in cytochrome P-450-ligand interaction following phenobarbital.... Xenobiotica. 1972; 2(1):89-99. DOI: 10.3109/00498257209036237. View

Couvaris M, Galanopoulou P, Karageorgiou C, Theodosopoulos S, Varonos D . Comparative study of the effects of some inducers with or without protein binding properties on bioavailability of isoxazolylpenicillins in rats. Eur J Drug Metab Pharmacokinet. 1986; 11(3):187-94. DOI: 10.1007/BF03189846. View

Tuano S, Johnson L, BRODIE J, KIRBY W . Comparative blood levels of hetacillin, ampicillin and penicillin G. N Engl J Med. 1966; 275(12):635-9. DOI: 10.1056/NEJM196609222751203. View

Bennett J, BRODIE J, BENNER E, KIRBY W . Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol. 1966; 14(2):170-7. PMC: 546645. DOI: 10.1128/am.14.2.170-177.1966. View

Nousiainen U, Hanninen O . On the inducibility of cytosolic and microsomal carboxylesterase by phenobarbital in rat tissues. Acta Pharmacol Toxicol (Copenh). 1981; 49(1):77-80. DOI: 10.1111/j.1600-0773.1981.tb00873.x. View

KIRBY W, Kind A . Clinical pharmacology of ampicillin and hetacillin. Ann N Y Acad Sci. 1967; 145(2):291-7. DOI: 10.1111/j.1749-6632.1967.tb50226.x. View

Penttila O, Neuvonen P, Aho K, LEHTOVAARA R . Interaction between doxycycline and some antiepileptic drugs. Br Med J. 1974; 2(5917):470-2. PMC: 1610633. DOI: 10.1136/bmj.2.5917.470. View

Galanpoulou P, Karageorgiou C, Kouvaris M, Varonos D . Influence of liver enzyme induction caused by phenobarbital on the biotransformation of hetacillin in male rats. J Antimicrob Chemother. 1980; 6(1):157-9. DOI: 10.1093/jac/6.1.157. View

BREYER U . Perazine, chlorpromazine and imipramine as inducers of microsomal drug metabolism. Naunyn Schmiedebergs Arch Pharmacol. 1972; 272(3):277-88. DOI: 10.1007/BF00499039. View

10.

Stevenson I, OMalley K, Turnbull M, Ballinger B . The effect of chlorpromazine on drug metabolism. J Pharm Pharmacol. 1972; 24(7):577-8. DOI: 10.1111/j.2042-7158.1972.tb09060.x. View

11.

Pelkonen O, Sotaniemi E, Ahokas J . Coumarin 7-hydroxylase activity in human liver microsomes. Properties of the enzyme and interspecies comparisons. Br J Clin Pharmacol. 1985; 19(1):59-66. PMC: 1463777. DOI: 10.1111/j.1365-2125.1985.tb02613.x. View

12.

BUSFIELD D, CHILD K, Atkinson R, TOMICH E . AN EFFECT OF PHENOBARBITONE ON BLOOD-LEVELS OF GRISEOFULVIN IN MAN. Lancet. 1963; 2(7316):1042-3. DOI: 10.1016/s0140-6736(63)90012-6. View

13.

Couvaris M, Galanopoulou P, Karageorgiou C, Jalil H, Varonos D . Bioavailability of hetacillin in rats after liver enzyme induction by various inducers with or without protein binding properties. Eur J Drug Metab Pharmacokinet. 1985; 10(1):27-32. DOI: 10.1007/BF03189694. View

14.

Marsh C . Metabolism of d-glucuronolactone in mammalian systems. Identification of d-glucaric acid as a normal constituent of urine. Biochem J. 1963; 86(1):77-86. PMC: 1201715. DOI: 10.1042/bj0860077. View

15.

Ohnhaus E, Park B . Enzyme-inducing drug combinations and their effects on liver microsomal enzyme activity in man. Eur J Clin Pharmacol. 1983; 24(2):247-50. DOI: 10.1007/BF00613826. View

16.

Perucca E, Hedges A, Makki K, Ruprah M, Wilson J, Richens A . A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol. 1984; 18(3):401-10. PMC: 1463658. DOI: 10.1111/j.1365-2125.1984.tb02482.x. View

17.

BUSFIELD D, CHILD K, TOMICH E . AN EFFECT OF PHENOBARBITONE ON GRISEOFULVIN METABOLISM IN THE RAT. Br J Pharmacol Chemother. 1964; 22:137-42. PMC: 1703912. DOI: 10.1111/j.1476-5381.1964.tb01551.x. View

18.

Neuvonen P, Penttila O . Interaction between doxycycline and barbiturates. Br Med J. 1974; 1(5907):535-6. PMC: 1633645. DOI: 10.1136/bmj.1.5907.535. View