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Titolo:
POPULATION PHARMACOKINETICS OF LAMOTRIGINE MONOTHERAPY IN PATIENTS WITH EPILEPSY - RETROSPECTIVE ANALYSIS OF ROUTINE MONITORING DATA
Autore:
HUSSEIN Z; POSNER J;
Indirizzi:
UNIV MANCHESTER,SCH PHARM & PHARMACEUT SCI,CTR APPL PHARMACOKINET RES,OXFORD RD MANCHESTER M13 9PL LANCS ENGLAND
Titolo Testata:
British journal of clinical pharmacology
fascicolo: 5, volume: 43, anno: 1997,
pagine: 457 - 465
SICI:
0306-5251(1997)43:5<457:PPOLMI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
ADD-ON TRIAL; PARTIAL SEIZURES; BW430C;
Keywords:
LAMOTRIGINE; EPILEPSY; MONOTHERAPY; NONMEM; POPULATION; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
20
Recensione:
Indirizzi per estratti:
Citazione:
Z. Hussein e J. Posner, "POPULATION PHARMACOKINETICS OF LAMOTRIGINE MONOTHERAPY IN PATIENTS WITH EPILEPSY - RETROSPECTIVE ANALYSIS OF ROUTINE MONITORING DATA", British journal of clinical pharmacology, 43(5), 1997, pp. 457-465

Abstract

Aims To examine the population pharmacokinetics of lamotrigine in patients newly diagnosed with epilepsy and receiving oral lamotrigine monotherapy for up to 48 weeks. Methods The population consisted of 158 Caucasians and 5 Asians of whom 81 were males and 82 females. Age and weight ranged between 14 and 76 years and 41-107 kg, respectively. A one-compartment compartment model with first-order absorption and elimination was fitted to plasma lamotrigine concentration-time profiles from retrospective drug monitoring, using non-linear mixed effect modelling (NONMEM), with first-order estimation. Oral clearance (CLo), apparent volume of distribution (V/F) and absorption rate constant (K-a) were the main pharmacokinetic parameters. Results CLo was not significantly influenced by body weight, age, gender, oral contraceptives and dose. However, due to auto-induction CLo increased by 17.3% during the 48weeks of therapy, from 1.94 to 2.28 l h(-1), and was 28.7% lower in Asians than Caucasian. The final magnitude in interpatient variability was 32%. The effect of the covariates weight, age, race and gender on V/F was examined and none was statistically significant. The final population estimate of V/F was 77.41 with an interpatient variability of 34%. Conclusions In view of the wide therapeutic margin of lamotrigineand the 21% residual variability in plasma concentrations, the modestsignificant effects of race and auto-induction on clearance are unlikely to be clinically significant and, thus, no dosage adjustment is warranted for these effects.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 00:40:44