Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects.

Abstract

1 Stereoselectivity in the pharmacokinetics of nitrendipine was investigated by re-analysing plasma samples of a previously published study (Soons et al., 1989 4 The clearance of intravenously administered (S)-nitrendipine was slightly (7%) lower than that of (R)-nitrendipine, but elimination half-lives and volumes of distribution were similar. 5 The difference in disposition of nitrendipine enantiomers is most likely related to a difference in activity of the cytochrome P-450 system towards the enantiomers, giving rise to a two-fold difference in first-pass elimination. 6 Stereoselectivity in the first pass metabolism of nitrendipine exhibited little intersubject variability and therefore is not a major factor in the wide variability in systemic availability of the more-potent (S)-enantiomer.

Effect of Crystal Size on the In Vitro Dissolution and Oral Absorption of Nitrendipine in Rats

“…Its octanol-water distribution coefficient (log P oct ) is 3.59 (17), and it is classified as a Class II active pharmaceutical ingredient (API) by the BCS. The absolute oral bioavailability of this drug is reported to range from about 10% to 20%, depending in part on the dosage form (18,19). The dissolution is the rate-limiting factor for absorption.…”

Enantioselective pharmacokinetics of the enantiomers of clevidipine following intravenous infusion of the racemate in essential hypertensive patients

“…Differences between the pharmacokinetics of the separate enantiomers have been reported for several calcium antagonists of the dihydropyridine type. [16][17][18][19] These studies mainly investigated the pharmacokinetics of the separate enantiomers following administration of the racemic mixture. Following racemic nitrendipine administration in man, Soons and Breimer 16 reported that the difference between the pharmacokinetics of nitrendipine enantiomers was much smaller when racemate was administered intravenously instead of orally.…”

Bunazosin in patients with impaired hepatic or renal function

“…In the case of vasodilating compounds, such as calcium antagonists or ui-blockers, an increased responsiveness of the hepatic blood vessels to high concentrations of these drugs during the absorption phase may be a contributing factor for our observation. Thereby the temporarily increased liver blood flow might reduce presystemic elimination resulting in a rise in bioavailability of, for example, bunazosin (17,18). This has also been suggested to be a major detenninant for the variability of nisoldipine pharmacokinetics (18).…”

“…Thereby the temporarily increased liver blood flow might reduce presystemic elimination resulting in a rise in bioavailability of, for example, bunazosin (17,18). This has also been suggested to be a major detenninant for the variability of nisoldipine pharmacokinetics (18).…”