Impact of a Four‐Day Head‐Down Tilt (–6°) on Lidocaine Pharmacokinetics Used as Probe to Evaluate Hepatic Blood Flow

The impact of a microgravity simulation using a head‐down tilt (–6°) on lidocaine pharmacokinetics used as a probe to evaluate hepatic blood flow is discussed. Eight healthy male subjects were selected for a 7‐day study, including a 4‐day head‐down tilt from day 2 to day 5. Subjects were given 1 mg/kg of lidocaine on days 1 through 5 and 7. Blood sampling, cardiac output, and hepatic artery blood flow velocity measurements were done within 6 hours after administration. Cardiac output increased significantly during head‐down tilt, and returned to basal values during the recovery period. Blood flow velocity in the hepatic artery increased during the first day of the down tilt. Slight side effects (buzzing noise in the ears and sleepy feeling) were reported within minutes after the injection of lidocaine. Lidocaine disposition was modified during head‐down tilt: a significant decrease in maximal concentration (1.47 ± 0.26 mg/L on day 1 and 0.96 ± 0.30 mg/L on day 2); an increase in elimination clearance from 8.24 ± 3.22 mL/kg • minutes −1 to 11.63 ± 3.00 mL/kg • minutes −1 ; an increase in volume of distribution on day 2 and a decrease to lower than basal value on the other days (2.77 ± 1.73 L/kg on day 1 and 2.33 ± 0.48 L/kg on day 7). Half‐life regularly decreased from 264 ± 210 minutes to 160 ± 60 minutes between day 1 and day 7. With the exception of day 1, no correlation was found between blood flow in the hepatic artery and lidocaine clearance, probably owing to the lack of precision of echo Doppler measurement, which only permitted indirect assessment. The reported pharmacokinetic modifications suggested that the dosage of drugs such lidocaine must be adapted during long‐term administration in microgravity conditions by increasing the dose or reducing the interval of drug intake.