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Titolo:
DIETARY SALT INCREASES FIRST-PASS ELIMINATION OF ORAL QUINIDINE
Autore:
DARBAR D; DELLORTO S; MORIKE K; WILKINSON GR; RODEN DM;
Indirizzi:
VANDERBILT UNIV,SCH MED,DIV CLIN PHARMACOL,532 MED RES BLDG 1 NASHVILLE TN 37232 VANDERBILT UNIV,SCH MED,DEPT MED NASHVILLE TN 37232 VANDERBILT UNIV,SCH MED,DEPT PHARMACOL NASHVILLE TN 37232
Titolo Testata:
Clinical pharmacology and therapeutics
fascicolo: 3, volume: 61, anno: 1997,
pagine: 292 - 300
SICI:
0009-9236(1997)61:3<292:DSIFEO>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
ERYTHROMYCIN BREATH TEST; P-GLYCOPROTEIN; SMALL-BOWEL; INTESTINAL-ABSORPTION; EXTRAHEPATIC TISSUES; DRUG-METABOLISM; CYTOCHROME-P-450; RAT; LIVER; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
D. Darbar et al., "DIETARY SALT INCREASES FIRST-PASS ELIMINATION OF ORAL QUINIDINE", Clinical pharmacology and therapeutics, 61(3), 1997, pp. 292-300

Abstract

Background: Some cytochrome P450 (CYP) enzymes, including CYP3A, are expressed not only in the liver but also in the intestine; the latter may therefore be an important site of drug disposition. Animal data suggests that dietary salt modulates expression of renal CYPs. We therefore hypothesized that intestinal CYP3A may be similarly modulated by dietary salt. Methods: The effect of changes in dietary salt on the disposition of two CYP3A substrates, quinidine (administered orally and intravenously) and C-14-erythromycin (administered intravenously) were determined after normal volunteers were given high-salt (400 mEq/day) and low-salt (10 mEq/day) diets for 7 to 10 days each. Results: Plasmaconcentrations after oral quinidine were significantly lower during the high-salt phase, with the difference between the two treatments attributable to changes within the first 1 to 4 hours after administration, For example, the area under the plasma concentration-time curve forthe first hour after drug administration was 0.56 +/- 0.38 mu g . hr/ml for the high-salt diet compared with 1.57 +/- 0.60 mu g . hr/ml forthe low-salt diet (p < 0.05). Similarly, the peak plasma concentration (C-max) achieved was lower and the time to reach C-max was later forthe high-salt diet (p < 0.05). In contrast, the terminal phase elimination half-lives were similar for the two diets, and no differences indisposition were found with the intravenous drug. The erythromycin breath test was unaffected by the dietary treatments. Conclusions: Theseresults indicate an effect of dietary salt on the presystemic disposition of orally administered quinidine. Although the mechanism(s) of CYP3A activity modulation is unknown, this finding may be important in determining drug availability in conditions associated with abnormal salt homeostasis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 02:24:57