The pharmacokinetics of a single dose of gentamicin (4 mg/kg) as prophylaxis in cardiac surgery requiring cardiopulmonary bypass.
BACKGROUND
Cardiopulmonary bypass has complex effects on drug pharmacokinetics, which is important when considering the use of once-daily aminoglycoside regimens during cardiac surgery.


OBJECTIVE
To study the effects of cardiopulmonary bypass on the pharmacokinetics of a single dose of gentamicin (4 mg/kg).


METHODS
Nine patients undergoing valve replacement surgery were given a single dose of gentamicin (4 mg/kg) at induction of anaesthesia and blood was taken for assay at 0, O.5, 1, 1.5, 2, 2.5, 3, 4, 6, 10, 16, 22 and 24 h following administration. The mean (range) gentamicin Cmax was 18.7 (12.4-26.3) mg/litre. Three patients had concentrations of gentamicin after 24 h of > 1 mg/litre. During cardiopulmonary bypass, the mean (range) gentamicin half-life (t1/2) was 5.1 (2.0-15.1) h and post-bypass the t1/2 was 7.1 (3.0-13.9) h.


CONCLUSIONS
There is significant correlation between the elimination t1/2 and length of cardiopulmonary bypass (r = 0.89, P < 0.01). These results suggest that gentamicin excretion is delayed following cardiopulmonary bypass so that with dose regimens of > 4 mg/kg there is a risk of toxicity.
Lewis
D R
DR
Department of Surgery, Bristol Royal Infirmary, UK.
Longman
R J
RJ
Wisheart
J D
JD
Spencer
R C
RC
Brown
N M
NM
D000368:Aged; D019072:Antibiotic Prophylaxis / Q000379:methods*; D019540:Area Under Curve; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D005839:Gentamicins