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Metabolic disposition of proguanil in extensive and poor metabolisers of S-mephenytoin 4'-hydroxylation recruited from an Indonesian population. 1995

R Setiabudy, and M Kusaka, and K Chiba, and I Darmansjah, and T Ishizaki
Department of Pharmacology, Faculty of Medicine, University of Indonesia, Jakarta.

1. The metabolism of proguanil (PG) was studied by measuring PG, cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) in plasma and urine samples after an oral 200 mg dose of PG hydrochloride administered to 14 extensive (EMs) and 10 poor hydroxylators (PMs) of S-mephenytoin of Indonesian origin. 2. The mean ( +/- s.d.) values of the elimination half-life (t 1/2) and AUC of PG were significantly (P < 0.01) greater in the PM than in the EM group (20.6 +/- 3.1 vs 14.6 +/- 3.5 (95% confidence intervals of difference 3.1 to 8.9) h; and 5.43 +/- 1.89 vs 3.68 +/- 0.83 (0.58 to 2.91) micrograms ml-1 h). 3. Plasma concentrations of CG, an active metabolite, could not be detected in all PMs, and those of CPB were sufficiently high to determine a time-course in only four PMs. Mean AUC(0,24 h) values of CPB were significantly (P < 0.05) lower in the PM (n = 4) than in the EM group (n = 14) (0.47 +/- 0.13 vs 0.88 +/- 0.50 (-0.14 to 0.96) micrograms ml-1 h). 4. Log10 percentage urinary recovery of 4'-hydroxymephenytoin correlated significantly (P < 0.05) with the t 1/2 (rs = -0.661) and AUC (rs = -0.652) of PG. 5. PG, CG and CPB were detectable in urine at 12 h in all subjects. Log10 percentage urinary recovery of 4'-hydroxymephenytoin correlated significantly (P < 0.01) with urinary PG/CG (rs = -0.876), PG/CPB (rs = -0.833) and PG/(CG + CPB) (rs = -0.831) metabolic ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007214 Indonesia A republic stretching from the Indian Ocean east to New Guinea, comprising six main islands: Java, Sumatra, Bali, Kalimantan (the Indonesian portion of the island of Borneo), Sulawesi (formerly known as the Celebes) and Irian Jaya (the western part of New Guinea). Its capital is Djakarta. The ethnic groups living there are largely Chinese, Arab, Eurasian, Indian, and Pakistani; 85% of the peoples are of the Islamic faith. Celebes,Indonesian New Guinea,Irian Jaya,Java,Madoera,Netherlands East Indies,New Guinea, Indonesian,New Guinea, West,Sulawesi,Sumatra,Timor,West Irian,Bali,East Indies,Madura,Malay Archipelago
D008297 Male Males
D008617 Mephenytoin An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias. Methoin,Methyl Phenetoin,5-Ethyl-3-Methyl-5-Phenylhydantoin,Mefenetoin,Mesantoin,Phenantoin,5 Ethyl 3 Methyl 5 Phenylhydantoin,Phenetoin, Methyl
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D002727 Proguanil A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent. Chlorguanid,Chloroguanide,Bigumal,Chloriguane,Chloroguanide Hydrochloride,Paludrin,Paludrine,Proguanil Hydrochloride,Hydrochloride, Chloroguanide,Hydrochloride, Proguanil
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes

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