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Arzneimittelforschung 2009; 59(3): 117-120
DOI: 10.1055/s-0031-1296373
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Comparative Bioavailability of Propafenone after Administration of a Magistral Suspension vs. Commercial Tablets in Healthy Volunteers

Hugo Juárez Olguín
1   Laboratorio de Farmacologia, Instituto Nacional de Pediatria, Mexico City, (Mexico)
2   Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autönoma de Mexico, México City, (Mexico)
,
Carmen Flores Pérez
1   Laboratorio de Farmacologia, Instituto Nacional de Pediatria, Mexico City, (Mexico)
,
Bianca Ramírez Mendiola
1   Laboratorio de Farmacologia, Instituto Nacional de Pediatria, Mexico City, (Mexico)
,
Lina Barranco Garduño
2   Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autönoma de Mexico, México City, (Mexico)
,
Eunice Sandoval Ramírez
1   Laboratorio de Farmacologia, Instituto Nacional de Pediatria, Mexico City, (Mexico)
,
Janett Flores Pérez
1   Laboratorio de Farmacologia, Instituto Nacional de Pediatria, Mexico City, (Mexico)
2   Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autönoma de Mexico, México City, (Mexico)
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Publikationsverlauf

Publikationsdatum:
13. Dezember 2011 (online)

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Abstract

Propafenone (CAS 34183-22-7) is an effective antiarrhythmic drug used in children, although in some countries no specific pediatric formulation is available. The aim of this study is to compare the relative bioavailability of a magistral (MAG) preparation of propafenone versus its commercial (COM) presentation in a group of 16 Mexican healthy volunteers. Bioavailability was determined after crossover administration of the drugs, through a randomized two-phase trial. All volunteers had normal hepatic and renal functions, determined clinically at the beginning of the study, and received 150 mg of either COM (tablets) or MAG (suspension). Blood samples were drawn for a 24-h post-dose analysis by HPLC to measure plasma levels of propafenone. Subjects (mean 25.9 ± 5.3 years and 66.1 ± 12.4 kg) had the following pharmacokinetic parameters: Cmax 189.9 ± 20.92 ng/mL, Tmax 1.5 h, AUC 322.4 ± 36.28 ng • ml1 • h for COM. Values for MAG were Cmax 225.8 ± 24.38 ng/mL, Tmax 1.7 h and AUC 359.3 ± 27.90 ng • ml1 • h. These values yielded a relative bioavailability of 111.42 % for MAG compared with COM. No electrocardiographic changes were recorded in any subject with respect to the baseline value, in both treatment schemes. Therefore, propafenone suspension prepared as a magistral formulation may be used as an alternative drug in pediatric patients.

Key words

Antiarrhythmics - CAS 34183-22-7 - Propafenone, bioavailability, healthy volunteers, hospital pharmacy, pharmacokinetics
 

  • References

  • 1 Bink-Boelkens MT. Pharmacologic management of arrhythmias. Pediatr Cardiol. 2000; 21: 508-15
    CrossrefPubMedGoogle Scholar
  • 2 Connolly S, Cynthia L, Winkle A, Harrison D, Kates R. Propafenone disposition kinetics in cardiac arrhytmia. Clin Pharmacol Ther. 1984; 36: 163-68
    CrossrefPubMedGoogle Scholar
  • 3 Capucci A, Villani GQ, Aschieri D, Piepoli M. Safety of oral propafenone in the conversion of recent onset atrial fibrillation to sinus rhythm: a prospective parallel placebo-controlled multicentre study. Int J Cardiol. 1999; 68: 187-96
    CrossrefPubMedGoogle Scholar
  • 4 Vozeh S, Heafeli W, Ha HR, Vlcek j, Follath F. Nonlinear kinetics of propafenone metabolites in healthy man. Eur J Clin Pharmacol. 1990; 38: 509-13
    CrossrefPubMedGoogle Scholar
  • 5 Siddowey IA, McAllister CB, Wang T, Bergstrand RH, Roden DM, Wilkinson GR et al. Polymorphic axidative metabolism of propafenone in man. Circulation. 1983; 68 (Suppl 3)
    PubMedGoogle Scholar
  • 6 Carvalho PR, Carvalho CG, Alievi PT, Martinbiancho J, Trotta EA. Prescription of drugs not appropriate for children in a Pediatric Intensive Care Unit. J Pediatr (Rio J). 2003; 79: 397-402
    CrossrefPubMedGoogle Scholar
  • 7 Chen B, Cai WM. Influence of CYP2D6*10B genotype on pharmacokinetics of propafenone enantiomers in Chinese subjects. Acta Pharmacol Sin. 2003; 24: 1277-80
    PubMedGoogle Scholar
  • 8 Johnson CE, Streetman DD. Stability of oral suspensions of ursodiol made from tablets. Am J Health Syst Pharm. 2002; 59: 361-3
    PubMedGoogle Scholar
  • 9 VandenBussche HL, Jonhson CE, Fontana EM, Meran JM. Stability of levofloxasin in an extemporaneously compounded oral liquid. Am J Health Syst Pharm. 1999; 56: 2316-8
    PubMedGoogle Scholar
  • 10 Olguín Juárez H, Pérez Flores C, Pérez Flores J, Mendiola Ramírez B, Portugal Carrasco M, Chavez Bobadilla J. Bioavailability of an extemporaneous suspension of propafenone made from tablets. Biopharm Drug Dispos. 2006; 27: 241-5
    CrossrefPubMedGoogle Scholar
  • 11 Flores Pérez C, Juárez Olguín H, Flores Pérez J, Ramirez Mendiola B, Bobadilla Chávez J. A simple method to measure plasma levels of propafenone with fluorescence detection. Chromatographia. 2005; 62: 373-7
    CrossrefPubMedGoogle Scholar
  • 12 Win-Nonlin program, Standard edition, version 1.1. Mountain View, CA: Scientific Consulting Inc.; 1991
    PubMed
  • 13 Bauer LA. Clinical Pharmacokinetics and Pharmacodynamics. In: Dipiro JT. et al. (editors). Pharmacotherapy. 6th ed. New York: McGraw-Hill; 2005: 51-74
    Google Scholar
  • 14 Wong A. The inappropriate usage and adverse effects of drugs in clinical practice. J Pediatr (Rio J). 2003; 79: 379-80
    CrossrefPubMedGoogle Scholar
  • 15 Sasaki S, Kuomi S, Sato R. Kinetics of buccal absorption of propafenone single oral loading dose in healthy humans. Gen Pharmacol. 1998; 31: 589-91
    CrossrefPubMedGoogle Scholar
  • 16 Cai Wei-Min, Zang Yin-Di, Chen Bing, Cai Ming-Hong, Luo Jian-Ping, Ling Shu-Sen. Simultaneous modeling of pharmacokinetics and pharmacodynamics of propafenone in healthy subjects. Acta Pharmacol Sin. 2001; 10: 956-60
    PubMedGoogle Scholar
  • 17 Minoo A, Mohammadreza R. A rapid HPLC assay for the simultaneous determination of propafenone and its major metabolites in human serum. Anal Sci. 2004; 20: 1307-11
    CrossrefPubMedGoogle Scholar