Download PDF
Arzneimittelforschung 2011; 61(8): 444-451
DOI: 10.1055/s-0031-1296226
Antihypertensives
Editio Cantor Verlag Aulendorf (Germany)

Pharmacokinetics of felodipine extended-release tablets in healthy Taiwanese subjects: a retrospective review

Hsiao Chia-Ling
1   College of Pharmacy, Taipei Medical University, Taipei, Taiwan
2   Division of Preclinical Science, Center for Drug Evaluation, Taipei, Taiwan
,
Wu Ya-Chi
3   Division of Clinical Science, Center for Drug Evaluation, Taipei, Taiwan
,
Hsu Kuang-Yang
1   College of Pharmacy, Taipei Medical University, Taipei, Taiwan
› Author Affiliations
Further Information

Publication History

Publication Date:
27 November 2011 (online)

    Permissions and Reprints

Abstract

The objective of this study was to investigate the pharmacokinetics of felodipine (CAS 72509-76-3) in healthy male Taiwanese subjects. This is a retrospective review of five felodipine pharmacokinetic studies completed in Taiwan. A total of 100 evaluable healthy Taiwanese males were enrolled in these studies. The subjects received 5 mg (n = 80) or 10 mg (n = 20) of Plendil® (felodipine extended-release tablets; felodipine ER) once daily for 6 days. The mean ± SD tmax, ss, Cmax, ss and AUCτ of dose normalized to 10 mg felodipine was 3.32 ± 1.33 h, 13.12 ± 5.34 nmol/L and 136.33 ± 63.18 nmol · h/L, respectively. By using Kolmogorov-Smirnov’s test and probit plots, the results indicated that the frequency distribution of AUC/dose, Cmin/ dose and CL/F was bimodal. Compared to data from the literature, the mean Cmax, ss and AUCτ of 5 mg felodipine in healthy young Taiwanese subjects were similar to or slightly lower than data from Swedish, Danish, Turkish and Canadian studies in healthy young subjects who received 10 mg felodipine. Comparable Cmax values and approximately 30% lower AUC values were observed when comparing the 5 mg Taiwanese data to data in healthy elderly German subjects who also received 5 mg felodipine. Taiwanese subjects might have lower CYP3A4 activity to metabolize felodipine, which is similar to the phenomenon observed with nifedipine.

Key words

Antihypertensive drug - Calcium-channel blocker - Felodipine - Pharmacokinetics - Taiwanese
 

  • References

  • 1 Ljung B. Vascular selectivity of felodipine. Drugs. 1985; 29 (Suppl 2) 46-58
    CrossrefPubMedSearch in Google Scholar
  • 2 Edgar B, Regårdh CG, Johnsson G, Johansson L, Lundborg P, Löfberg I et al Felodipine kinetics in healthy men. Clin Pharmacol Ther. 1985; Aug 38 (2) 205-11
    CrossrefPubMedSearch in Google Scholar
  • 3 Sutfin TA, Lind T, Gabrielsson M, Regårdh CG. Biliary secretion of felodipine metabolites in man after intravenous [14C]felodipine. Eur J Clin Pharmacol. 1990; 38 (5) 421-4
    CrossrefPubMedSearch in Google Scholar
  • 4 Edgar B, Hoffmann KJ, Lundborg P, Regårdh CG, Rönn O, Weidolf L. Absorption, distribution and elimination of felodipine in man. Drugs. 1985; 29 (2) 9-15
    PubMedSearch in Google Scholar
  • 5 Edgar B, Regårdh CG, Lundborg P, Romare S, Nyberg G, Rönn O. Pharmacokinetic and pharmacodynamic studies of felodipine in healthy subjects after various single, oral and intravenous doses. Biopharm Drug Dispos. 1987; May–Jun; 8 (3) 235-48
    CrossrefPubMedSearch in Google Scholar
  • 6 Hasselgren B, Ronn O, Edgar B, Johansson P, Wall B. Pharmacokinetics and hemodynamic and diuretic/natriuretic effects of felodipine administered as an extended-release tablet. Cardiovasc Drugs Ther. 1990; Dec; 4 (6) 1495-500
    CrossrefPubMedSearch in Google Scholar
  • 7 Blychert E, Hedner T, Dahlof C, Elmfeldt D. Plasma concentration-effect relationships of intravenous and extended-release oral felodipine in hypertensive patients. J Cardiovasc Pharmacol. 1990; Mar; 15 (3) 428-35
    CrossrefPubMedSearch in Google Scholar
  • 8 Elmfeldt D, Bengtsson B, Edgar B, Moberg L, Ronn O. Pharmacokinetics and haemodynamics of felodipine in hypertensive patients treated concomitantly with a betablocker. Drugs. 1987; 34 (3) 30
    CrossrefPubMedSearch in Google Scholar
  • 9 Regardh CG, Baarnhielm C, Edgar B. Pharmacokinetics and biotransformation of 1,4-dihydropyridine calcium channel antagonists. Prog Drug Metab. 1991; 12: 41-86
    PubMedSearch in Google Scholar
  • 10 Guengerich FP, Brian WR, Iwasaki M, Sari MA, Baarnhielm C, Berntsson P. Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4. J Med Chem. 1991; 34: 1838-44
    CrossrefPubMedSearch in Google Scholar
  • 11 Blychert E, Edgar B, Elmfeldt D, Hedner T. Plasma concentration-effect relationships for felodipine: a meta analysis. Clin Pharmaco Ther. 1992; 52: 80-9
    PubMedSearch in Google Scholar
  • 12 Landahl S, Edgar B, Gabrielsson M, Larsson M, Lernfeit B, Lundborg P et al Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects. Clin Pharmacokinet. 1998; 14: 374-83
    PubMedSearch in Google Scholar
  • 13 Dunselman PH, Edgar B, Scaf AH, Kuntze CE, Wesseling H. Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure. Br J Clin Pharmacol. 1989; 28: 45-52
    CrossrefPubMedSearch in Google Scholar
  • 14 Regardh CG, Edgar B, Olsson R, Kendall M, Collste P, Shansky C. Pharmacokinetics of felodipine in patients with liver disease. Eur J Clin Pharmacol. 1989; 36: 473-9
    CrossrefPubMedSearch in Google Scholar
  • 15 Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet. 1997; 32: 210-58
    CrossrefPubMedSearch in Google Scholar
  • 16 Ahsan CH, Renwick AG, Macklin B, Challenor VF, Waller DG, George CF. Ethnic differences in the pharmacokinetics of oral nifedipine. Br J Clin Pharmacol. 1991; 31: 399-403
    CrossrefPubMedSearch in Google Scholar
  • 17 Yu KS, Cho JY, Shon JH, Bae KS, Yi SY, Lim HS et al Ethnic differences and relationships in the oral pharmacokinetics of nifedipine and erythromycin. Clin Pharmacol Ther. 2001; 70: 228-36
    CrossrefPubMedSearch in Google Scholar
  • 18 Chien SC, Uang YS, Lin HY, Hsu KY. Pharmacokinetics of nifedipine in Taiwanese. Biopharm Drug Dispos. 2004; 25: 77-84
    CrossrefPubMedSearch in Google Scholar
  • 19 Kleinbloesem CH, van BP, Faber H, Danhof M, Vermeulen NP, Breimer DD. Variability in nifedipine pharmacokinetics and dynamics: a new oxidation polymorphism in man. Biochem Pharmacol. 1984; 33: 3721-4
    CrossrefPubMedSearch in Google Scholar
  • 20 Hoyo-Vadillo C, Castaneda-Hernandez G, Herrera JE, Vidal-Garate J, Moreno-Ramos A, Chavez F et al Pharmacokinetics of nifedipine slow release tablet in Mexican subjects: further evidence for an oxidation polymorphism. J Clin Pharmacol. 1989; 29: 816-20
    PubMedSearch in Google Scholar
  • 21 Schellens JH, Soons PA, Breimer DD. Lack of bimodality in nifedipine plasma kinetics in a large population of healthy subjects. Biochem Pharmacol. 1988; 37: 2507-10
    CrossrefPubMedSearch in Google Scholar
  • 22 Zhu B, Liu ZQ, Chen GL, Chen XP, Ou-Yang DS, Wang LS et al The distribution and gender difference of CYP3A activity in Chinese subjects. Br J Clin Pharmacol. 2003; 55: 264-9
    CrossrefPubMedSearch in Google Scholar
  • 23 Edgar B, Lundborg P, Regardh CG. Clinical pharmacokinetics of felodipine. A summary. Drugs. 1987; 34 (3) 16-27
    CrossrefPubMedSearch in Google Scholar
  • 24 Daly AK, Cholerton S, Gregory W, Idle JR. Metabolic polymorphisms. Pharmacol Ther. 1993; 57: 129-60
    CrossrefPubMedSearch in Google Scholar
  • 25 Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD. Ery-thromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. Clin Pharmacol Ther. 1996; 60: 25-33
    CrossrefPubMedSearch in Google Scholar
  • 26 Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit juice-felodipine interaction: effect of naringin and 6’,7’-dihydroxybergamottin in humans. Clin Pharmacol Ther. 1998; 64: 248-56
    CrossrefPubMedSearch in Google Scholar
  • 27 Guo LQ, Chen QY, Wang X, Liu YX, Chu XM, Cao XM et al Different roles of pummelo furanocoumarin and cytochrome P450 3A5*3 polymorphism in the fate and action of felodipine. Curr Drug Metab. 2007; 8: 623-30
    CrossrefPubMedSearch in Google Scholar
  • 28 Blychert E, Wingstrand K, Edgar B, Lidman K. Plasma concentration profiles and antihypertensive effect of conventional and extended-release felodipine tablets. Br J Clin Pharmacol. 1990; 29: 39-45
    CrossrefPubMedSearch in Google Scholar
  • 29 Madsen JK, Jensen JD, Jensen LW, Pedersen EB. Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine. Eur J Clin Pharmacol. 1996; 50: 203-8
    CrossrefPubMedSearch in Google Scholar
  • 30 Aberg J, Abrahamsson B, Grind M, Nyberg G, Olofsson B. Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers. Eur J Clin Pharmacol. 1997; 52: 471-7
    CrossrefPubMedSearch in Google Scholar
  • 31 Lundahl J, Regardh CG, Edgar B, Johnsson G. Effects of grapefruit juice ingestion-pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol. 1997; 52: 139-45
    CrossrefPubMedSearch in Google Scholar
  • 32 Gelal A, Balkan D, Ozzeybek D, Kaplan YC, Gurler S, Guven H et al Effect of menthol on the pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol. 2005; 60: 785-90
    CrossrefPubMedSearch in Google Scholar
  • 33 Lin KM, Lau JK, Smith R, Phillips P, Antal E, Poland RE. Comparison of alprazolam plasma levels in normal Asian and Caucasian male volunteers. Psychopharmacology. 1988; 96: 365-9
    CrossrefPubMedSearch in Google Scholar
  • 34 Kang YS, Park SY, Yim CH, Kwak HS, Gajendrarao P, Krishnamoorthy N et al The CYP3A4*18 genotype in the cytochrome P450 3A4 gene, a rapid metabolizer of sex steroids, is associated with low bone mineral density. Clin Pharmacol Ther. 2009; 85: 312-8
    CrossrefPubMedSearch in Google Scholar
  • 35 Yamamoto T, Nagafuchi N, Ozeki T, Kubota T, Ishikawa H, Ogawa S et al CYP3A4*18: it is not rare allele in Japanese population. Drug Metab Pharmacokinet. 2003; 18: 267-8
    CrossrefPubMedSearch in Google Scholar
  • 36 Lee SJ, Lee SS, Jeong HE, Shon JH, Ryu JY, Sunwoo YE et al The CYP3A4*18 allele, the most frequent coding variant in asian populations, does not significantly affect the midazolam disposition in heterozygous individuals. Drug Metab Dispos. 2007; 35: 2095-101
    CrossrefPubMedSearch in Google Scholar
  • 37 Hu YF, He J, Chen GL, Wang D, Liu ZQ, Zhang C et al CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms in a Chinese population. Clin Chim Acta. 2005; 353: 187-92
    CrossrefPubMedSearch in Google Scholar
  • 38 Xie HG, Kim RB, Wood AJ, Stein CM. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol. 2001; 41: 815-50
    CrossrefPubMedSearch in Google Scholar
  • 39 Watts RW, Dufek A, Wing LM. Comparison of felodipine and enalapril monotherapy in essential hypertension. Blood Press. 1993; 2: 53-8
    CrossrefPubMedSearch in Google Scholar
  • 40 Littler WA. Control of blood pressure in hypertensive patients with felodipine extended release or nifedipine retard. Br J Clin Pharmacol. 1990; 30: 871-8
    CrossrefPubMedSearch in Google Scholar
  • 41 Zhu W, Li T, Ni C, Liu H, Fang L, Shang M et al Comparative study of barnidipine and felodipine in Chinese patients with essential hypertension. J Int Med Res. 2006; 34: 406-12
    PubMedSearch in Google Scholar
  • 42 Liau CS, Chien KL, Chao CL, Lee TM. Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients. J Int Med Res. 2002; 30: 330-6
    PubMedSearch in Google Scholar
  • 43 Cheung BM, Lau CP, Wu BZ. Amlodipine, felodipine, and isradipine in the treatment of Chinese patients with mild-to-moderate hypertension. Clin Ther. 1998; 20: 1159-69
    CrossrefPubMedSearch in Google Scholar
  • 44 Ueng KC, Chen ZC, Yeh PS, Hung KC, Hu SA, Hung YJ et al Nifedipine OROS in Chinese patients with hypertension-results of a post-marketing surveillance study in Taiwan. Blood Press. 2005; 14 (1) 32-38
    CrossrefPubMedSearch in Google Scholar
  • 45 Toal CB. Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg. Clin Ther. 2001; 23: 87-96
    CrossrefPubMedSearch in Google Scholar