OBJECTIVE: In a prior single-dose study that examined the effect of food on delavirdine pharmacokinetics in healthy volunteers, the absorption of delavirdine mesylate was delayed and the area under the curve was reduced by 26% in the presence of food. Since the complex, nonlinear pharmacokinetics of delavirdine do not permit a simple extrapolation of the results of a single-dose study to steady state, the present multiple-dose study was performed. PATIENTS AND STUDY DESIGN:Thirteen stable patients with HIV-1 infection (two females, 11 males; CD4 count range 124-588 cells/mm(3)) completed a randomised, crossover study in which subjects received two 14-day treatments with delavirdine mesylate 400mg every 8 hours. In treatment A, all delavirdine doses were administered on an empty stomach and in treatment B were taken with food. A pharmacokinetic evaluation was performed on day 14 of each treatment period. SETTING: An ambulatory AIDS research centre in an academic medical centre. INTERVENTIONS: Administration of delavirdine with and without food. MAIN OUTCOME MEASURES: Pharmacokinetic parameters for delavirdine. RESULTS: The maximum concentration (C(max)) [+/- standard deviation] in treatment A was 29.6 +/- 13.6muM and in treatment B it was 23.0 +/- 8.61muM (p = 0.037). The minimum concentrations (C(min)) were 9.45 +/- 6.7muM and 11.2 +/- 9.2muM, respectively (p > 0.05). The oral clearances (CL(oral)) were 17.8 +/- 41.6 L/h (treatment A) and 18.5 +/- 39.0 L/h (treatment B) [p > 0.05]. Similar patterns were observed for N-dealkylated delavirdine with a significant difference only in C(max) (4.13 vs 3.47muM [p = 0.022], treatment A vs B). CONCLUSIONS: These findings indicated that, in contrast to the increased CL(oral) noted in a prior single-dose study, food did not have a significant effect at steady state on the area under the plasma concentration-time curve or C(min). Although C(max) was significantly lower when the drug was taken taken with food, the clinical relevance of this parameter as compared with the trough concentration is unclear since the current focus for antiretrovirals is on maintaining trough concentrations in excess of in vitro inhibitory concentrations.
RCT Entities:
OBJECTIVE: In a prior single-dose study that examined the effect of food on delavirdine pharmacokinetics in healthy volunteers, the absorption of delavirdine mesylate was delayed and the area under the curve was reduced by 26% in the presence of food. Since the complex, nonlinear pharmacokinetics of delavirdine do not permit a simple extrapolation of the results of a single-dose study to steady state, the present multiple-dose study was performed. PATIENTS AND STUDY DESIGN: Thirteen stable patients with HIV-1 infection (two females, 11 males; CD4 count range 124-588 cells/mm(3)) completed a randomised, crossover study in which subjects received two 14-day treatments with delavirdine mesylate 400mg every 8 hours. In treatment A, all delavirdine doses were administered on an empty stomach and in treatment B were taken with food. A pharmacokinetic evaluation was performed on day 14 of each treatment period. SETTING: An ambulatory AIDS research centre in an academic medical centre. INTERVENTIONS: Administration of delavirdine with and without food. MAIN OUTCOME MEASURES: Pharmacokinetic parameters for delavirdine. RESULTS: The maximum concentration (C(max)) [+/- standard deviation] in treatment A was 29.6 +/- 13.6muM and in treatment B it was 23.0 +/- 8.61muM (p = 0.037). The minimum concentrations (C(min)) were 9.45 +/- 6.7muM and 11.2 +/- 9.2muM, respectively (p > 0.05). The oral clearances (CL(oral)) were 17.8 +/- 41.6 L/h (treatment A) and 18.5 +/- 39.0 L/h (treatment B) [p > 0.05]. Similar patterns were observed for N-dealkylated delavirdine with a significant difference only in C(max) (4.13 vs 3.47muM [p = 0.022], treatment A vs B). CONCLUSIONS: These findings indicated that, in contrast to the increased CL(oral) noted in a prior single-dose study, food did not have a significant effect at steady state on the area under the plasma concentration-time curve or C(min). Although C(max) was significantly lower when the drug was taken taken with food, the clinical relevance of this parameter as compared with the trough concentration is unclear since the current focus for antiretrovirals is on maintaining trough concentrations in excess of in vitro inhibitory concentrations.
Authors: C V Fletcher; E P Acosta; H Cheng; R Haubrich; M Fischl; R Raasch; C Mills; X J Hu; D Katzenstein; R P Remmel; R M Gulick Journal: AIDS Date: 2000-11-10 Impact factor: 4.177
Authors: M F Para; P Meehan; J Holden-Wiltse; M Fischl; G Morse; R Shafer; L M Demeter; K Wood; T Nevin; N Virani-Ketter; W W Freimuth Journal: Antimicrob Agents Chemother Date: 1999-06 Impact factor: 5.191
Authors: Mark J Shelton; Ross G Hewitt; John Adams; Andrew Della-Coletta; Steven Cox; Gene D Morse Journal: Antimicrob Agents Chemother Date: 2003-05 Impact factor: 5.191
Authors: Gene D Morse; Susan E Cohn; Mark J Shelton; Carol Greisberger; Steven R Cox; Andrew A Della-Coletta; William W Freimuth; Richard C Reichman Journal: Clin Drug Investig Date: 2003 Impact factor: 2.859