Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol

Abstract

A series of three-way crossover randomized studies were conducted to evaluate the absolute bioavailability of butorphanol, a potent agonist-antagonist analgesic, from transnasal, sublingual, and buccal disk formulations in order to identify a practical alternative to oral administration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingually or buccally. Serial blood samples were collected over 12 h and butorphanol plasma concentrations were determined by radioimmunoassay. The plasma concentration data were subjected to non-compartmental pharmacokinetic analysis. The elimination half-life of butorphanol was about 3-5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than that observed following sublingual or buccal administration. Mean absolute bioavailabilities of sublingual tablet and buccal disk formulation were only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol was selected for further clinical trials of treatment of moderate to severe pain.

EVALUATION OF CARDIORESPIRATORY, BLOOD GAS, AND LACTATE VALUES DURING EXTENDED IMMOBILIZATION OF WHITE RHINOCEROS (CERATOTHERIUM SIMUM)

“…As a nasal preparation, hypotension did not occur with any appreciable frequency (Gillis et al, 1995). No change in cardiac or vital signs were observed in volunteers receiving multiple doses of 1-4 mg for 16 days (Shyu et al, 1993). Interestingly, butorphanol (1.5-6 mg/70 kg, i.m.)…”

“…Sublingual tablet and buccal disk formulations only increased mean absolute bioavailability to 19 and 29% (Shyu et al, 1993). Peak plasma concentrations of 2.2 ng/mL butorphanol occur between 30-60 min after a single 2-mg i.m.…”

“…Peak plasma concentrations of 0.9-1.04 ng/mL butorphanol occur 30-60 min after a single 1-mg i.m. administration (Shyu et al, 1993;Vachharajani et al, 1997a;Vachharajani et al, 1997b). The mean elimination half-life of transnasal butorphanol is 47 min -5.8 h in healthy volunteers; 6.6 h in the elderly; and 8.6-10.5 h in patients with renal impairment (Gillis et al, 1995).…”

“…With transnasal administration, butorphanol bioavailability increases to 48-70% (Shyu et al, 1993;Gillis et al, 1995). Transnasal butorphanol was well-tolerated by all subjects and plasma concentrations and AUCs increased in a dose-dependent manner indicating linear kinetics.…”

Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects

“…To the best of our knowledge, there are no published studies comparing the PK of supralingually versus sublingually administered pharmaceutic agents, whereas several studies, mainly involving opioid analgesics [6][7][8][9], have assessed the PK and bioequivalence of buccal versus sublingual administration. These studies demonstrate that bioequivalence between these two routes is highly dependent on the agent being assessed.…”