The metabolic disposition of ¹⁴C-ciramadol in humans

Abstract

1. Twelve subjects received single 15 mg oral doses of ¹⁴C-ciramadol. Excretion of the dose occurred almost entirely by the renal route (93.5 ± 11.7 (S.D.)% of the dose), and only 0.7±0.6% of the dose was recovered in faeces indicating that absorption was essentially complete. More than 90% of the amount recovered in urine was excreted within 24 h after dosing.

2. Unchanged drug accounted for 43.9 ± 6.5% of the dose, while a phenolic glucuronide conjugate was the only major urinary metabolite accounting for a further 37.9 ± 7.8%. A second glucuronide that was conjugated with the alicyclic ring was also identified but constituted only 2.3±0.6% of the dose.

3. Concentrations of radioactivity in plasma reached a peak at 2h after dosing and declined with a terminal disposition half life of 4.9h. Only ciramadol and the aryl-O-glucuronide were detected in substantial amounts in plasma.

4. Renal clearance of ciramadol amounted to 298±54 ml/min suggesting tubular secretion in addition to glomerular filtration.

Key Words:

• biotransformation
• ¹⁴C-ciramadol
• excretion balance
• glucuronidation
• plasma kinetics