Impact of a four-day head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as probe to evaluate hepatic blood flow.
The impact of a microgravity simulation using a head-down tilt (-6 degrees) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Saivin
S
S
Laboratoire de Pharmacocinétique et Toxicologie Clinique, Hôpital Rangueil, Toulouse, France.
Pavy-Le Traon
A
A
Cornac
A
A
Güell
A
A
Houin
G
G
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D018475:Head-Down Tilt; D006801:Humans; D008012:Lidocaine / Q000493:pharmacokinetics*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D008012:Lidocaine