Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Dose-dependent pharmacokinetics and metabolism of valproic acid in newbornlambs and adult sheep
Autore:
Wong, H; Rurak, DW; Kumar, S; Kwan, E; Abbott, FS; Riggs, KW;
Indirizzi:
Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada Univ British Columbia Vancouver BC Canada V6T 1Z3 ver, BC V6T 1Z3, Canada Univ British Columbia, British Columbia Res Inst Childrens & Womens Hlth, Dept Obstet & Gynecol, Fac Med, Vancouver, BC V6T 1Z3, Canada Univ British Columbia Vancouver BC Canada V6T 1Z3 ver, BC V6T 1Z3, Canada
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 5, volume: 29, anno: 2001,
pagine: 664 - 675
SICI:
0090-9556(200105)29:5<664:DPAMOV>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMA-PROTEIN BINDING; GUINEA-PIGS; SERUM-PROTEINS; DISPOSITION; DRUG; CLEARANCE; FETAL; RAT; ELIMINATION; PHARMACODYNAMICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Riggs, KW Univ British Columbia, Fac Pharmaceut Sci, 2146 East Mall, Vancouver, BC V6T 1Z3, Canada Univ British Columbia 2146 East Mall Vancouver BC Canada V6T 1Z3
Citazione:
H. Wong et al., "Dose-dependent pharmacokinetics and metabolism of valproic acid in newbornlambs and adult sheep", DRUG META D, 29(5), 2001, pp. 664-675

Abstract

Dose-dependent pharmacokinetics and metabolism of valproic acid (VPA) werestudied in newborn and adult sheep to assess age-related differences in plasma protein binding and metabolic elimination. Newborn lambs received either a 10- (n = 8), 50- (n = 5), 100- (n = 4), or 250-mg/kg (n = 4) VPA i.v. bolus. Individual adult sheep (n = 5) received all four doses in a random order with an appropriate washout period between experiments. Unbound or metabolic clearance of VPA was significantly higher in adult sheep at the two lower doses when compared with lambs, and similar to the lambs at the two higher doses. Plasma protein binding was nonlinear at all doses. Estimates of binding capacity (B-max1)at the saturable site were higher in adults (91.8 mug/ml) when compared with lambs (44.9 mug/ml), whereas the opposite trend was observed for binding affinity [K-d1 = 9.6 mug/ml (adult) versus 3.2 mug/ml (lambs)]. Characterization of developmental differences in overall VPA metabolic elimination involved fitting of unbound VPA plasma concentration data to a two-compartment model with Michaelis-Menten elimination. This resulted in similar in vivo estimates of apparent V-max [445.0 mug/min/kg (adult) versus 429.9 mug/min/kg (lambs)]. However, apparent K-m estimates appeared to be higher in lambs [30.0 mug/ml (adult) versus 69.6 mug/ml (lambs)]. Similar findings were obtained from in vivo estimates of V-max and K-m for VPA glucuronidation obtained from VPA-glucuronide metabolite urinary excretion data. Thus, it appears that age-related differences in metabolic clearance may be related to differences in the apparent in vivo K-m as opposedto V-max of VPA glucuronidation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 01:06:04