The pharmacokinetics of fluconazole were investigated in 18 disinfected subjects divided into two groups, group one 9 normal subjects {mean ± standard deviation age, 48.210 ± 7.390 year; weight, 76.890 ± 6.850 kg} and group two 9 patients with end – stage renal disease (ESRD) receiving long term thrice- weakly haemodialysis {mean ± standard deviation age, 53.415 ± 7.512 year; weight, 73.780 ± 4.270 kg} after the administration of a single oral 150 mg dose. For haemodialysis patients the study was done inter-dialysis i.e. day without dialysis and intra-dialysis i.e. during dialysis. Specific HPLC method and standard pharmacokinetic calculations were used to calculate fluconazole pharmacokinetic parameters. In healthy subjects, the peak plasma level (Cmax) averaged 956.231 ± 9.296 ng/ml and was obtained at 3 hr; the absorption rate constant (kab) was 1.675 ± 1.443h-1, the absorption half – life (t½ab) was 0.585 ± 0.288 hr. The elimination rate constant ( kel ) was 0.19 ± 0.003 h-1, the terminal half – life( t ½el) was 33.696± 4.333 hr. Area under the curve( AUC 0-72) was 17864.268 ± 731.527 ng/ml/hr and (AUC 0- ∞ ) was 25174.729 ± 1340.582 ng.ml/hr, total clearance rate was 0.099 ± 0.005 ml/min. In haemodialysis patients the peak plasma level (Cmax) averaged 947.410 ± 29.549 ng/ml and was obtained at 3.111 ± 0.333 hr; the absorption rate constant (kab) was 0.818 ± 0.887 h-1, the absorption half – life ( t½ab) was 1.286 ± 0.557 hr. The elimination rate constant( kel ) was 0.021 ± 0.003 h-1 , the terminal half – life( t ½) was 36.448 ± 3.896 hr. Area under the curve (AUC 0-72) was 33070 ± 11091.607ng.ml/hr, and( AUC 0-∞) was 48948.848 ± 4622.145 ng.ml/hr, respectively, total clearance rate(TCR) was 0.055 ± 0.005 ml/min . Some pharmacokinetic parameters during dialysis were determined as (K el ), (t½el ) and (Vd), also% Extraction Fraction (EF) during dialysis for each patient was calculated. Statistical analysis of pharmacokinetic data of the two groups revealed that renal failure did not significantly modify neither the peak plasma level nor the time to peak level. In renal failure patients there was significant increase at P < 0.01 in AUC0-72 and at P < 0.001in AUC72-∞, decrease in K el reflecting increase in t½el and significant increase in Vd and TCR both at P < 0.001. Fluconazole removed during haemodialysis and dosage adjustment in renal failure patients is essential.
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