Pharmacokinetics of the analogs at C3 and C5 of m-nifedipine in beagle dogs.

The prototype 1,4-dihydropyridine (1,4-DHP) nifedipine, indicated for the management of hypertension and angina pectoris, has disadvantages including photodegradation and a short half-life. Several newer 1,4-DHPs, including m-nifedipine and its analogs at the C3, C5 position such as MN9201, MN9202 and MN9203, have been designed to offset these problems. The aim of this study was to investigate the pharmacokinetic characteristics of these derivatives to provide reference for their further evaluation and modification. Derivatives were intravenously bolus administered to beagle dogs. The drug concentration in the plasma was determined by the HPLC method. The pharmacokinetic parameters were calculated by the non-compartmental method. The analysis of variance (ANOVA) was used to compare the pharmacokinetic parameters of the derivatives. The results showed that the area under the curve from time zero to the last sampling time (AUC(0-t)) of m-nifedipine, MN9201, MN9202 and MN9203 was 45.1 +/- 13.6, 51.7 +/- 15.2, 70 +/- 16 and 62 +/- 12.4 micromol/l*min, respectively. The elimination half-life (t(1/2)) was 98 +/- 24, 129 +/- 55, 190 +/- 21 and 92 +/- 25 min, respectively. The t(1/2) of MN9202 was significantly longer than those of the others (p<0.05 or p<0.01). These results suggest that the length of the carbon chain at the C3 or C5 position in the derivatives had a marked effect on its metabolism, and M9202 is a promising new drug candidate worth further evaluation.
AuthorsZhi-fu Yang, Si-yuan Zhou, Tie-hong Yang, Xin-you Liu, Qi-bing Mei
JournalBiopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 29 Issue 9 Pg. 485-94 (Dec 2008) ISSN: 1099-081X [Electronic] England
PMID19085951 (Publication Type: Journal Article)
CopyrightCopyright (c) 2008 John Wiley & Sons, Ltd.
Chemical References
  • 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester
  • Nifedipine
  • Animals
  • Area Under Curve
  • Dogs
  • Male
  • Molecular Structure
  • Nifedipine (analogs & derivatives, blood, chemistry, pharmacokinetics)
  • Reproducibility of Results

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