Pharmacokinetics of butorphanol nasal spray in patients with renal impairment

ABSTRACT

1The pharmacokinetics of butorphanol were evaluated in 18 female volunteers with varying degrees of renal function following a single, 1  mg transnasal dose of butorphanol tartrate. The creatinine clearance (CL_CR) values for subjects in the normal (NOR), moderately impaired (MI), and severely impaired (SI) groups were ≥70  ml min⁻¹, 30–60  ml min⁻¹, and ≤30  ml min⁻¹, respectively.

2Serial blood and urine samples were collected immediately after dosing for 48  h. Plasma concentrations of butorphanol were determined using a specific radioimmunoassay. Urine concentrations of butorphanol and its metabolites (hydroxy-butorphanol, norbutorphanol and their glucuronide conjugates) were determined using h.p.l.c. with fluorescence detection.

3There was no significant difference between the three treatments for peak plasma concentration of butorphanol and time to peak. Statistically significant differences were detected among the study groups for AUC, t_1/2, MRT, and CL_R with the mean values for severely impaired subjects significantly different from those of normal renal subjects; mean values for moderately impaired subjects were not significantly different from either the normal or severely impaired groups for all respective parameters.

4The elimination half-life of butorphanol increased from 5.75  h in NOR to 10.48  h in SI. A similar trend was observed for MRT. Creatinine clearance (CL_CR) significantly correlated with CL_R (r=0.563, P=0.019), CL_T/F (r=0.505, P=0.033), t_1/2 (r=−0.554, P=0.017) and λ (r=0.606, P=0.008).

5Although the exposure of butorphanol was greater in subjects with renal impairment, there was no trend for an increase in the number of adverse experiences reported by subjects with renal dysfunction.

6Patients with less than 30  ml min⁻¹ creatinine clearance may require less frequent administration of transnasal butorphanol as compared with subjects with normal or moderately impaired renal function.