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Titolo:
C-14-NAVP AND C-14-PEV REPEATED DOSE STUDY IN RAT PHARMACOKINETIC STUDY IN RATS AFTER REPEATED ORAL ADMINISTRATIONS OF C-14-VALPROIC ACID SODIUM-SALT AND C-14-VALPROIC ACID PIVALOYL OXYMETHYL ESTER
Autore:
BERTOLINO M; ACERBI D; CANALI S; GIACHETTI C; POLI G; VENTURA P; ZANOLO G;
Indirizzi:
RBM SPA,IST RIC BIOMED A MARXER,VIA RIBES 1 I-10010 COLLERETTO GIACOSTO ITALY CHIESI FARMACEUT SPA I-43100 PARMA ITALY
Titolo Testata:
European journal of drug metabolism and pharmacokinetics
fascicolo: 2, volume: 23, anno: 1998,
pagine: 223 - 229
SICI:
0378-7966(1998)23:2<223:CACRDS>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
VALPROIC ACID;
Keywords:
VALPROIC ACID; VALPROIC ACID PIVALOYL OXYMETHYL ESTER; RADIOACTIVITY; TISSUE DISTRIBUTION; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
6
Recensione:
Indirizzi per estratti:
Citazione:
M. Bertolino et al., "C-14-NAVP AND C-14-PEV REPEATED DOSE STUDY IN RAT PHARMACOKINETIC STUDY IN RATS AFTER REPEATED ORAL ADMINISTRATIONS OF C-14-VALPROIC ACID SODIUM-SALT AND C-14-VALPROIC ACID PIVALOYL OXYMETHYL ESTER", European journal of drug metabolism and pharmacokinetics, 23(2), 1998, pp. 223-229

Abstract

The absorption, excretion and tissue distribution of radioactivity after repeated oral equimolar doses of C-14-valproic acid sodium salt (NaVP) or C-14-valproic acid pivaloyl oxymethyl ester (PEV) was investigated in male rats treated once a day for 14 consecutive days. The 14thday plasma time-course of radioactivity after PEV administrations wascharacterised by a slow absorption rate with a delayed peak (tmax 2 h, Cmax 7.52 +/- 1.35 mu g eq./ml), followed by a plateau lasting up to8 h. After NaVP treatment, the main peak of radioactivity was observed 0.5 h after administration (Cmax 8.30 +/- 1.26 mu g eq./ml) followedby a secondary peak due to biliary enterohepatic recycling. Starting from 4 h onwards, radioactivity levels after PEV treatment were higherthan those af ter NaVP (AUC tau = 113.3 h.mu g eq./ml after PEV vs 71.9 h.mu g eq./ml after NaVP), but concentrations declined with similarterminal half-lives (52.8 h for PEV and 49.7 h for NaVP). Radioactivity recovered (0-432 h interval) in urine accounted for 79.3 % (PEV) and 56.1 % (NaVP) while, in faeces accounted for 9.1 % (PEV) and 26.1 % (NaVP) of total administered dose (14 days). The difference is attributable to a higher excretion of radioactivity in the bile for NaVP. Themissing fraction in the total radioactivity balance is probably excreted in expired air, as observed in single dose studies. Radioactivity excreted in bile (0-8 h interval of the last 14th day) accounted for 5.1% (NaVP) and 0.23% (PEV) of the total administered dose (14 days). Apossible explanation of this difference may be a different metabolismpattern for the two compounds. The negligible biliary excretion observed after PEV administration is probably due to an inhibition of the glucuronation of valproic acid (or other metabolites) caused by the pivalic acid. Due to the presence of the enterohepatic recycle, the radioactivity levels in intestine, 0.5 and 2 h after administration, were higher after NaVP administration. According to higher plasma levels, the radioactivity concentrations in liver, kidneys an d some fat tissueswere found to be slightly higher after PEV administration. At 120 h after the last treatment of both compounds, relevant tissue concentrations were observed in mesenteric lymphnodes, perirenal and brown fat. The tissue-plasma radio activity ratio appeared quite similar for the two compounds.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 06:15:55