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Titolo:
INHIBITION OF DIHYDROPYRIMIDINE DEHYDROGENASE BY 5-PROPYNYLURACIL, A METABOLITE OF THE ANTI-VARICELLA ZOSTER VIRUS AGENT NETIVUDINE
Autore:
PECK R; WIGGS R; CALLAGHAN J; WOOTTON R; CROME P; FRASER I; FRICK L; POSNER J;
Indirizzi:
WELLCOME RES FDN,DEPT CLIN PHARMACOL,LANGLEY COURT,S EDEN PK BECKENHAM BR3 3BS KENT ENGLAND WELLCOME RES LABS BECKENHAM BR3 3BS KENT ENGLAND KEELE UNIV,N STAFFORDSHIRE HOSP CTR,DEPT GERIATR MED STOKE ON TRENT ST4 STAFFS ENGLAND BURROUGHS WELLCOME CO RES TRIANGLE PK NC 27709
Titolo Testata:
Clinical pharmacology and therapeutics
fascicolo: 1, volume: 59, anno: 1996,
pagine: 22 - 31
SICI:
0009-9236(1996)59:1<22:IODDB5>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL PYRIMIDINEMIA; 5-FLUOROURACIL; TOXICITY; BROMOVINYLDEOXYURIDINE; 5-ETHYNYLURACIL; DEFICIENCY; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
22
Recensione:
Indirizzi per estratti:
Citazione:
R. Peck et al., "INHIBITION OF DIHYDROPYRIMIDINE DEHYDROGENASE BY 5-PROPYNYLURACIL, A METABOLITE OF THE ANTI-VARICELLA ZOSTER VIRUS AGENT NETIVUDINE", Clinical pharmacology and therapeutics, 59(1), 1996, pp. 22-31

Abstract

Objective: To study the effects of the anti-herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5-propynyluracil. Methods: Three groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first doseand on days 2, 3, 5, 7, and 8, Pull plasma profiles of netivudine and5-propynyluracil were determined after the last dose.Results: Plasma uracil was unquantifiable in all subjects before the first dose and atall time points in the placebo group, In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 mu mol/L on day 8 in the subjects who received 400 and 800 mg, Plasma netivudine concentrations were approximately dose proportional, but 5-propynyluracil concentrations were similar in both groups, The half-maximal rise in plasma uracil occurred after a cumulative 5-propynyluracil exposure of 120 mu mol/L . hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily, Conclusions: Netivudinedosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase, Coadministration with the antimetabolite 5-fluorouracil willrequire a substantial reduction in 5-fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5-fluorouracil.

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Documento generato il 29/11/20 alle ore 10:08:44