Document Detail


Comparative bioavailability study of zidovudine administered as two different tablet formulations in healthy adult subjects.
MedLine Citation:
PMID:  16724579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: Zidovudine is a synthetic nucleoside analogue of thymidine with activity against the human immunodeficiency virus type 1 (HIV-1). In patients with HIV infections or the acquired immunodeficiency syndrome (AIDS), zidovudine is a first-line therapy that was shown to reduce morbidity, mortality, and hospitalization. A generic formulation of zidovudine offers the possibility of considerable savings to HIV/AIDS patients in developed and Third World countries. The objective of the current study was to characterize the pharmacokinetic and safety profiles of zidovudine administered as a generic tablet formulation relative to the innovator product. VOLUNTEERS AND METHODS: A total of 68 healthy adult volunteers received a 300 mg oral dose of zidovudine as the generic formulation (AVIRO-Z 300 mg tablet, Ranbaxy Laboratories Limited) and as the innovator product (Retrovir tablet, GlaxoSmithKline) in a randomized, 2-way crossover study. Multiple blood samples were collected over 12 hours and plasma concentrations of zidovudine were assayed using an LC/MS/MS method with an analytical range of 5.00 to 2,000 ng/ml. Pharmacokinetic parameters were calculated using non-compartmental methods. RESULTS: Mean plasma concentrations of zidovudine declined in a mono-exponential manner, with mean concentration values falling below the limit of quantitation 12 hours after administration of both formulations. Mean area under the curve from time 0 to the last measurable concentration (AUC(0-t)), mean area under the curve from time 0 to infinity (AUC(0-infinity)) and peak plasma concentrations (C(max)) of zidovudine for the generic tablet formulation (2,220.6 ng x h/ml, 2,236.0 ng x h/ml and 1,087.9 ng/ml, respectively) were very similar to those observed for the innovator product (2,139.7 ng x h/ml, 2,158.6 ng x h/ml and 1,066.5 ng/ml, respectively). Ratios of least-squares means and 90% confidence intervals of AUC(0-t) AUC(0-infinity) and C(max) between the 2 formulations were within 80-125%, suggesting that the two tablet formulations displayed similar rate and extent of bioavailability. The oral clearance (CL/F) of zidovudine for the generic and innovator formulations were 2.11 1/h/kg and 2.16 1/h/kg, respectively. For the two formulations, adverse events were similar in nature and frequency. CONCLUSION: Since the two formulations displayed similar in vivo delivery rate of zidovudine in the bloodstream, the generic tablet formulation of zidovudine developed by Ranbaxy should be equally effective as the innovator product and is expected to produce considerable cost-savings in AIDS patients worldwide.
Authors:
J F Marier; H Manthos; S Kebir; S Ferron; M DiMarco; G Morelli; S K Tippabhotla; T Vijan; A K Singla; M Garg; T Monif
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  International journal of clinical pharmacology and therapeutics     Volume:  44     ISSN:  0946-1965     ISO Abbreviation:  Int J Clin Pharmacol Ther     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-26     Completed Date:  2007-07-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9423309     Medline TA:  Int J Clin Pharmacol Ther     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  240-6     Citation Subset:  IM    
Affiliation:
MDS Pharma Services, Montreal, Quebec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Biological Availability
Chemistry, Pharmaceutical
Drugs, Generic / administration & dosage,  pharmacokinetics*
Female
Humans
Male
Middle Aged
Reverse Transcriptase Inhibitors / administration & dosage,  blood,  pharmacokinetics*
Tablets
Zidovudine / administration & dosage,  blood,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/Drugs, Generic; 0/Reverse Transcriptase Inhibitors; 0/Tablets; 30516-87-1/Zidovudine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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