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B Avni

Publications and source records attributed to B Avni.

3 recordsLinked to original sources
PubMed2001

Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers.

Grapefruit juice (GJ), a cytochrome P450 (CYP) 3A4 inhibitor, may affect the pharmacokinetics of drugs metabolized through CYP 3A4. Losartan, an angiotensin II antagonist, is converted into its main active metabolite E3174 by CYP 3A4 and CYP 2C9. The effect of GJ on losartan pharmacokinetics was assessed in a randomized crossover trial. Losartan was given to 9 volunteers with and without GJ. Concentrations of losartan and its E3174 metabolite were determined in serum by a high-performance liquid chromatography method (HPLC). Significant differences were observed in some of the pharmacokinetic parameters of losartan and its metabolite E3174 after losartan administration with and without co-administered GJ. The lag time (time to drug appearance in serum) of losartan increased significantly with co-administered GJ. The mean residence time (MRT) and half-life (t(1/2)) of the E3174 metabolite were significantly longer and the area under the concentration--time curve (AUC) of the E3174 metabolite was significantly smaller after concomitant GJ administration. The ratio AUC(losartan)/AUC(E3174) was significantly increased after concurrent grapefruit juice intake. The increased lag time of losartan and the increased MRT and t1/2 and decreased AUC of E3174 were considered indicative of simultaneous CYP 3A4 inhibition and P-glycoprotein activation. The significantly increased AUC(losartan)/AUC(E3174) ratio, however, indicates reduced losartan conversion to E3174 by CYP 3A4 metabolism as a result of co-administered GJ.

Adult↗
PubMed1998

Octreotide ameliorates glucose intolerance following acute experimental pancreatitis.

The long-term effects of octreotide, the synthetic analog of the hormone somatostatin, on acute experimental pancreatitis were studied. Acute pancreatitis was induced in rats by intraparenchymal injections of 0.5 ml 5% or 10% sodium taurocholate. Octreotide (10 mg/kg/day, subcutaneously), or saline injections as controls, were started four hours later, and their effects were assessed 30, 60, and 90 days after the induction of pancreatitis. Neither intrapancreatic saline injections nor octreotide administration without the induction of pancreatitis caused any biochemical or histological abnormalities. Taurocholate-induced pancreatitis was followed by remarkable hyperglycemia, which was ameliorated by octreotide. Thirty days after induction of pancreatitis, glucose levels were 269+/-21 mg/100 ml and 153+/-17 mg/100 ml in the control and octreotide treated animals, respectively (P < 0.02). Octreotide administration was associated with increased pH values after 60 and 90 days (P < 0.05 for the 90 days group). The levels of hematocrit, calcium, and amylase were already within the normal ranges after 30 days and were unaffected by octreotide. There were no signs of chronic exocrine insufficiency and all the surviving rats gained weight during the follow-up. However, the relative weights of the pancreases of the octreotide-treated animals were higher than those of the controls 30 days after IOP. Histopathological evaluation demonstrated regeneration of the pancreatic tissue, and increased number and hypertrophy of the islets of Langherhans. There were no significant differences whether the octreotide treatment was given for only 48 or 96 hr. Survival was significantly improved by octreotide; only one octreotide-treated rat (2.5%) with 10% taurocholate-induced pancreatitis died, while six (15%) of the control animals succumbed (P < 0.05). These studies provided data on the sequelae of acute pancreatitis and showed that octreotide may have long-term beneficial effects in this disease.

Acute Disease↗