PMID- 23084093
OWN - NLM
STAT- MEDLINE
DCOM- 20130521
LR  - 20221207
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 11
DP  - 2012 Nov
TI  - Pharmacokinetic properties and bioequivalence of two sulfadoxine/pyrimethamine 
      fixed-dose combination tablets: a parallel-design study in healthy Chinese male 
      volunteers.
PG  - 2212-20
LID - S0149-2918(12)00563-2 [pii]
LID - 10.1016/j.clinthera.2012.10.001 [doi]
AB  - BACKGROUND: Sulfadoxine/pyrimethamine fixed-dose combination (FDC) tablet is the 
      long-acting portion of the antimalaria product Artecospe((R)), 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 x 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 (C(max), AUC(0-72), AUC(0-168), and T(max)) were calculated and 
      analyzed statistically. The 2 formulations were to be considered bioequivalent if 
      90% CIs for the log-transformed ratios of C(max) and AUC(0-72) 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 C(max) (183.07 and 165.15 mg/L), AUC(0-72) (11,036.52 and 
      10,536.78 mg/L/h), and AUC(0-168) (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 C(max), AUC(0-72), and AUC(0-168) 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 
      bioequivalence. A total of 7 mild AEs were reported in 7 subjects (15.2%). 
      CONCLUSIONS: The findings from this single-dose (1500/75-mg) study suggest that 
      the test and reference formulations of sulfadoxine/pyrimethamine FDC 500/25-mg 
      tablet have similar pharmacokinetic profiles both in terms of rate and extent of 
      absorption. The formulations met WHO's and China's FDA regulatory criteria for 
      bioequivalence in these healthy Chinese volunteers under fasting conditions. Both 
      formulations were generally well-tolerated.
CI  - Copyright (c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Liu, Yan-Mei
AU  - Liu YM
AD  - Phase I Clinical Research Unit, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Zhang, Kanyin E
AU  - Zhang KE
FAU - Liu, Yun
AU  - Liu Y
FAU - Zhang, Hai-Chen
AU  - Zhang HC
FAU - Song, Yun-Xiao
AU  - Song YX
FAU - Pu, Hua-Hua
AU  - Pu HH
FAU - Lu, Chuan
AU  - Lu C
FAU - Liu, Gang-Yi
AU  - Liu GY
FAU - Jia, Jing-Ying
AU  - Jia JY
FAU - Zheng, Qing-Si
AU  - Zheng QS
FAU - Zhu, Jian-Min
AU  - Zhu JM
FAU - Yu, Chen
AU  - Yu C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antimalarials)
RN  - 0 (Drug Combinations)
RN  - 0 (Drugs, Generic)
RN  - 0 (Tablets)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Analysis of Variance
MH  - Antimalarials/administration & dosage/adverse 
      effects/blood/chemistry/*pharmacokinetics
MH  - *Asian People
MH  - Chemistry, Pharmaceutical
MH  - Chi-Square Distribution
MH  - China
MH  - Chromatography, Liquid
MH  - Drug Combinations
MH  - Drugs, Generic/administration & dosage/adverse 
      effects/chemistry/*pharmacokinetics
MH  - Humans
MH  - Indicator Dilution Techniques
MH  - Linear Models
MH  - Male
MH  - Mass Spectrometry
MH  - Middle Aged
MH  - Models, Biological
MH  - Pyrimethamine/administration & dosage/adverse 
      effects/blood/chemistry/*pharmacokinetics
MH  - Sulfadoxine/administration & dosage/adverse 
      effects/blood/chemistry/*pharmacokinetics
MH  - Tablets
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2012/10/23 06:00
MHDA- 2013/05/23 06:00
CRDT- 2012/10/23 06:00
PHST- 2012/08/22 00:00 [received]
PHST- 2012/09/26 00:00 [revised]
PHST- 2012/10/01 00:00 [accepted]
PHST- 2012/10/23 06:00 [entrez]
PHST- 2012/10/23 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
AID - S0149-2918(12)00563-2 [pii]
AID - 10.1016/j.clinthera.2012.10.001 [doi]
PST - ppublish
SO  - Clin Ther. 2012 Nov;34(11):2212-20. doi: 10.1016/j.clinthera.2012.10.001. Epub 
      2012 Oct 17.