Diurnal variation in the biliary excretion of flomoxef in patients with percutaneous transhepatic biliary drainage.
OBJECTIVE
To examine diurnal variation in biliary excretion of flomoxef.


METHODS
Flomoxef (1 g) was injected intravenously in eight patients with percutaneous transhepatic cholangiography with drainage at 09.00 h and 21.00 h by a cross-over design with a 36 h washout period. Drained biliary fluid was collected for 6 h after each dosing. These patients still had mild to moderate hepatic dysfunction.


RESULTS
Bile flow and bile acid excretion for 6 h after dosing did not differ significantly between the 09.00 h and 21.00 h treatments. The maximum concentration of biliary flomoxef was significantly greater and its total excretion for 6 h tended to be greater after the 21.00 h dose [maximum concentration (microg ml(-1)): 34.2 +/- 29.9 (09.00 h dose) vs 43.5 +/- 28.3 (21.00 h dose) (95% confidence interval for difference: 2.6 approximately 15.9, P = 0.013); total excretion (mg 6 h(-1)): 1.4 +/- 1.3 (09.00 h dose) vs 1.6 +/- 1.2 (21.00 h dose) (95% confidence interval for difference: -26.8, 313.7, P = 0.087)]. The period that biliary flomoxef remained above the minimal inhibitory concentration did not differ significantly between the two treatment times.


CONCLUSIONS
These results suggest that biliary excretion of flomoxef shows diurnal variation. However, as the difference was relatively small, flomoxef could be given at any time of day without any dosage adjustments.
Hishikawa
S
S
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Kobayashi
E
E
Sugimoto
K
K
Miyata
M
M
Fujimura
A
A
D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts; D002511:Cephalosporins / Q000493:pharmacokinetics*; D002758:Cholangiography / Q000379:methods; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism*; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D015641:Radiography, Interventional
D001647:Bile Acids and Salts; D002511:Cephalosporins; C045693:flomoxef