G J Merritt1, J B Slade. 1. Department of Hyperbaric Medicine, David Grant USAF Medical Center, Travis AFB, California.
Abstract
STUDY OBJECTIVE: To determine the single-dose pharmacokinetics of gentamicin in healthy humans undergoing hyperbaric oxygen (HBO) exposure. DESIGN: Randomized, crossover trial. SETTING: Specialized hyperbaric research facility within a United States Air Force medical center. SUBJECTS:Five healthy men between 28 and 43 years of age. INTERVENTIONS: Each subject received a total of two doses of intravenous gentamicin 1.5 mg/kg lean body weight spaced at least 2 weeks apart. One dose was infused under normobaric oxygen (NBO) conditions and the other under HBO conditions. MEASUREMENTS AND MAIN RESULTS:Gentamicin pharmacokinetic values were determined on 11 serum samples per subject collected sequentially out to 300 minutes after infusion. Using PCNONLIN, the following results demonstrated no difference between the pharmacokinetic values under HBO and NBO conditions, respectively: beta half-life (112, 115 min); volume of distribution (0.201, 0.184 L/kg); peak concentration (6.52, 7.23 mg/L); clearance (0.0754, 0.0676 L/kg/hr). CONCLUSIONS:Hyperbaric oxygen produced no changes in the measured pharmacokinetic values of gentamicin under the conditions specified in this study. It is possible that numerous HBO exposures could produce a cumulative effect on gentamicin pharmacokinetics that would not be discernible in a single-dose study. Because of the profound physiologic effects of HBO, drugs with narrow therapeutic indexes should be evaluated under HBO conditions if they are to be given to patients receiving HBO treatments.
RCT Entities:
STUDY OBJECTIVE: To determine the single-dose pharmacokinetics of gentamicin in healthy humans undergoing hyperbaric oxygen (HBO) exposure. DESIGN: Randomized, crossover trial. SETTING: Specialized hyperbaric research facility within a United States Air Force medical center. SUBJECTS: Five healthy men between 28 and 43 years of age. INTERVENTIONS: Each subject received a total of two doses of intravenous gentamicin 1.5 mg/kg lean body weight spaced at least 2 weeks apart. One dose was infused under normobaric oxygen (NBO) conditions and the other under HBO conditions. MEASUREMENTS AND MAIN RESULTS:Gentamicin pharmacokinetic values were determined on 11 serum samples per subject collected sequentially out to 300 minutes after infusion. Using PCNONLIN, the following results demonstrated no difference between the pharmacokinetic values under HBO and NBO conditions, respectively: beta half-life (112, 115 min); volume of distribution (0.201, 0.184 L/kg); peak concentration (6.52, 7.23 mg/L); clearance (0.0754, 0.0676 L/kg/hr). CONCLUSIONS: Hyperbaric oxygen produced no changes in the measured pharmacokinetic values of gentamicin under the conditions specified in this study. It is possible that numerous HBO exposures could produce a cumulative effect on gentamicin pharmacokinetics that would not be discernible in a single-dose study. Because of the profound physiologic effects of HBO, drugs with narrow therapeutic indexes should be evaluated under HBO conditions if they are to be given to patients receiving HBO treatments.