Bioavailability and disposition of terodiline in man.
Terodiline was concomitantly administered intravenously (12.5 mg) and orally ([2H]terodiline, 12.5 mg) to 10 healthy volunteers. In four of the subjects, a tracer dose of the intravenously given terodiline was 3H-labeled. In a separate study, six subjects were given [3H]terodiline orally. Estimated pharmacokinetic parameters were as follows: systemic clearance, 93 mL/min; renal clearance, 14 mL/min; volume of distribution at steady-state, 407 L; terminal half-life, 54 h; and mean residence time, 77 h. After intravenous infusion, a rapid distribution phase (half-life, 4.5 min) could be observed. The maximum serum concentration after the oral dose was 29 micrograms/L and the time to maximum concentration was 5 h (estimated by noncompartmental analysis). Absorption commenced within the first hour and by deconvolution the maximum rate of absorption was determined to occur between 1 and 3 h, and by 3.4 h 90% of the available dose had been absorbed. Calculation of bioavailability by noncompartmental AUC, two-compartmental analysis, urinary excretion, and 24-h oral/intravenous concentration ratio gave similar results (ANOVA test, not significant). About 75% and 25% of administered radioactivity could be recovered in urine and feces, respectively. Intact terodiline in feces accounted for about 1% of the dose. p-Hydroxyterodiline was quantitated in feces and accounted for about 5% of the dose. Another metabolite, 3,4-dihydroxyterodiline, which has not previously been detected in urine or serum, was also identified.
Hallén
B
B
Kabi Pharmacia AB, Department of Pharmacokinetics, Stockholm, Sweden.
Karlsson
M O
MO
Stromberg
S
S
Norén
B
B
D000284:Administration, Oral; D001682:Biological Availability; D001711:Biotransformation; D002082:Butylamines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D006801:Humans; D007262:Infusions, Intravenous; D007408:Intestinal Absorption; D008875:Middle Aged
D002082:Butylamines; D002121:Calcium Channel Blockers; C010637:terodiline