Pharmacokinetic Properties and Bioequivalence of Two Sulfadoxine/Pyrimethamine Fixed-Dose Combination Tablets: A Parallel-Design Study in Healthy Chinese Male Volunteers

Abstract Background Sulfadoxine/pyrimethamine fixed-dose combination (FDC) tablet is the long-acting portion of the antimalaria product Artecospe® , coblister containing artesunate tablets plus sulfadoxine/pyrimethamine FDC tablets. This study was conducted to support the efficacy and tolerability o...

Full description

Saved in:
Bibliographic Details
Published in:Clinical therapeutics 2012-11, Vol.34 (11), p.2212-2220
Main Authors: Liu, Yan-Mei, MD, Zhang, Kanyin E., PhD, Liu, Yun, MD, Zhang, Hai-Chen, MD, Song, Yun-Xiao, MD, Pu, Hua-Hua, MD, Lu, Chuan, BS, Liu, Gang-Yi, MS, Jia, Jing-Ying, MS, Zheng, Qing-Si, MS, Zhu, Jian-Min, MD, Yu, Chen, MS
Format: Article
Language:English
Subjects:
Administration, Oral
Adolescent
Adult
Analysis of Variance
Antimalarials - administration & dosage
Antimalarials - adverse effects
Antimalarials - blood
Antimalarials - chemistry
Antimalarials - pharmacokinetics
Asian Continental Ancestry Group
bioequivalence
Biological and medical sciences
Chemistry, Pharmaceutical
Chi-Square Distribution
China
Chromatography, Liquid
Dihydrofolate reductase
Drug Combinations
Drug dosages
Drug therapy
Drugs, Generic - administration & dosage
Drugs, Generic - adverse effects
Drugs, Generic - chemistry
Drugs, Generic - pharmacokinetics
Hepatitis
Hospitals
Humans
Indicator Dilution Techniques
Internal Medicine
LC-IDMS
Linear Models
Malaria
Male
Mass Spectrometry
Medical Education
Medical sciences
Middle Aged
Models, Biological
parallel design
Parasites
pharmacokinetic
Pharmacology. Drug treatments
pyrimethamine
Pyrimethamine - administration & dosage
Pyrimethamine - adverse effects
Pyrimethamine - blood
Pyrimethamine - chemistry
Pyrimethamine - pharmacokinetics
sulfadoxine
Sulfadoxine - administration & dosage
Sulfadoxine - adverse effects
Sulfadoxine - blood
Sulfadoxine - chemistry
Sulfadoxine - pharmacokinetics
Tablets
Therapeutic Equivalency
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background Sulfadoxine/pyrimethamine fixed-dose combination (FDC) tablet is the long-acting portion of the antimalaria product Artecospe® , coblister containing artesunate tablets plus sulfadoxine/pyrimethamine FDC tablets. This study was conducted to support the efficacy and tolerability of the sulfadoxine/pyrimethamine FDC tablet in the World Health Organization's (WHO) Prequalification of Medicines Programme, as well as to obtain marketing authorization in China. Objective The aim of the present study was to compare the pharmacokinetic profiles between a new generic and the branded reference formulation of sulfadoxine/pyrimethamine FDC tablets, and to assess the bioequivalence of the 2 products in healthy Chinese volunteers. Methods This single-dose, open-label, randomized, parallel-group study was conducted in healthy Chinese male volunteers who were randomly assigned (1:1) to receive a single 1500/75-mg dose (3 × 500/25-mg tablets) of either the test or reference formulation after a 12-hour overnight fast. Seventeen blood samples were obtained over a 168-hour interval, and plasma concentrations of sulfadoxine and pyrimethamine were determined by 2 separate validated liquid chromatography–isotopic dilution mass spectrometry methods. Pharmacokinetic properties (Cmax , AUC0–72 , AUC0–168 , and Tmax ) were calculated and analyzed statistically. The 2 formulations were to be considered bioequivalent if 90% CIs for the log-transformed ratios of Cmax and AUC0–72 were within the predetermined bioequivalence range of 80% to 125%, in accordance with the guidelines of WHO and China's Food and Drug Administration (FDA). Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead ECGs, and subject interviews on adverse events (AEs). Results Forty-six healthy subjects completed the study. The mean values of sulfadoxine Cmax (183.07 and 165.15 mg/L), AUC0–72 (11,036.52 and 10,536.78 mg/L/h), and AUC0–168 (22,247.05 and 21,761.02 mg/L/h) were not significantly different between the test and reference formulations, respectively. The same was true for pyrimethamine (0.55 and 0.58 mg/L, 29.85 and 31.44 mg/L/h, and 56.18 and 59.27 mg/L/h, respectively). The 90% CIs for the log-transformed ratios of Cmax , AUC0–72 , and AUC0–168 of both sulfadoxine (105.4%–116.6%, 99.3%–110.6%, and 96.4%–108.1%) and pyrimethamine (88.8%–100.9%, 89.5%–101.0%, and 88.3%–101.6%) were within the acceptance limits for bioeq
ISSN:0149-2918
1879-114X
DOI:10.1016/j.clinthera.2012.10.001