ABSTRACT
Objective: To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1. Methods: A single nucleotide polymorphism of ABCB1 3435C>T (rs1045642) in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment. Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration. The relationship between plasma efavirenz concentrations and ABCB1 3435C>T polymorphisms was analyzed. Results: Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age, gender, body weight, CD4 count and plasma HIV-1 RNA, blood biochemical parameters, antiretroviral duration or ABCB1 3435C>T polymorphisms, except for height (OR=0.902, 95% CI: 0.835-0.973) (PT was 0.446. The frequency of the heterozygous mutant ABCB1 3435C/ T was 53.02% (n=79), ABCB1 3435T/T homozygous mutant was 18.12% (n=27) and the wild type ABCB1 3435C/C genotype was 28.86% (n=43). The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L [IQR: (1.46-4.12) mg/L]. The plasma concentration of efavirenz was higher in cases with ABCB1 3435T/T homozygous mutant [2.73 mg/L, IQR: (2.02-4.19) mg/L] and ABCB1 3435C/T heterozygous mutant [2.29 mg/L, IQR: (1.41-4.28) mg/L] genotypes compared to the wild type ABCB1 3435C/C homozygous [2.1 mg/L, IQR: (1.37-3.53) mg/L]. However, there was no statistically significant difference in the efavirenz concentration between the different genotypes (P>0.05). Conclusions: There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB1 3435T/T and ABCB1 3435C/T genotypes. No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.
ABSTRACT
Abstract Comparison of Amphotericin B Induced Nephrotoxicity between 6 Hours vwesus 24 Hours Continuous Infusion: A Randomized Controlled Trial On-umar Banpamai MD* Kumthorn Malathum MD*** Somnuek Domrongkitchaiporn MD*** Weerawat Manosuthi MD**** Sasivimol Rattanasiri MSc (Biostatistics)***** *Division of Infectious Diseases, Department of Medicine, BMA Medical College and Vajira Hospital **Division of Infectious Diseases, Department of Medicine, Ramathibodi Hospital, Mahidol Unrversity ***Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Mahidol Unrversity **** Department of Medicine, Bamrasnaradura Institute *****Clinical Epidemiology Unit, Ramathibodi Hospital, Mahidol Unrversity Objective: To compare nephrotoxicity and infusion-related reactions between 6 hours versus 24 hours infusion of amphotericin B. Study design: Prospective, randomized controlled study. Subjects: Seventy-two patients who required amphotericin B therapy for various indications, between August 2004 and March 2005 at Department of Medicine, Ramathibodi Hospital and Bamrasnaradura Institute were randomly allocated to receive either 6 hours or 24 hours infusion of amphotericin B. Methods: Thirty-five patients received continuous infusion of amphotericin B for a period of 6 hours as a control group and 37 patients for a period of 24 hours as a study group. Creatinine clearance, serum potassium (k+), serum magnesium ( Mg+ ), fractional excretion of potassium and magnesium were determined in all patients once a week. Infusion-related side effects of both regimens were also recorded throughout the study. Main outcome measures: Creatinine clearance at 7 and 14 days after receiving amphotericin B, infusion-related side effects, fractional excretion of potassium and magnesium. Results: Creatinine clearance at day 7 and day 14 in study group were 83.922.9 and 81.822.5 ml/min. In control group, creatinine clearance at day 7 and day 14 were 62.7 25.3 and 51.718.9 ml/min. These levels in study group were higher than control group significantly (p-value 0.05). The incidence of renal impairment, defined as doubling of baseline serum creatinine, in study and control group were 2.7% and 45.7% that was different significantly (p-value 0.001). The incidences of infusion-related reactions other than thrombophlebitis were significantly lower in study group. Fractional excretion of statistically different between the two groups. Conclusion: The creatinine clearance, the incidence of renal impairment and infusion-related reactions in continuous 24-hour infusion of amphotericin B were lower than 6-hour infusion. Key word: amphotericin B, creatinine clearance, fractional excretion Vajira Med J 2006 ; 50 : 153 - 164