Radcliffe Infirmary, Oxford 1 A 10 h study of plasma drug concentrations of the opiate buprenorphine after sublingual use was designed because a previous 3 h study had shown that peak plasma drug concentrations in some patients had not occurred by 3 h after the sublingual dose. 2 Fifteen postoperative patients were studied: at 3 h after a 0.3 mg intravenous dose five patients received a sublingual preparation of 0.4 mg of buprenorphine, five 0.8 mg of buprenorphine and five placebo. Plasma drug concentrations of buprenorphine were measured by specific radioimmunoassay. 3 Plasma drug concentrations after sublingual buprenorphine were significantly higher than those in the placebo group by 1 h. They remained significantly higher over the succeeding nine hours. The mean time to peak plasma drug concentration was about 200 min in both the 0.4 mg and 0.8 mg groups (range 90-360 min). The plasma drug concentrations in the 0.8 mg group were approximately twice those in the 0.4 mg group; the ratio of the relative systemic availabilities was similarly 1.8:1. The absolute systemic availability was estimated at about 55% for both groups. Uptake of buprenorphine from the sublingual site was essentially complete by 5 h after the dose was given. 4 The implications for the timing of sublingual doses in clinical use are discussed.

1 Buprenorphine is a long‐acting opiate analgesic. This study was designed to investigate the pharmacokinetics of this drug when given by the sublingual route to ten postoperative patients. Plasma levels of buprenorphine were measured by a specific radioimmunoassay. 2 Plasma levels of the drug following sublingual administration of 0.4 mg showed an apparent delay in absorption and then rose slowly to reach low but significant levels by 3 h. There was considerable variation in the time at which peak levels were achieved. The average systemic availability of the drug by this route was estimated to be 30% by 3 h. 3 Analgesic efficacy and duration of sublingual buprenorphine were assessed using demand analgesia. The analgesia was of about 9 h duration, similar to that achieved by parenteral administration of 0.3 mg of the drug to an equivalent group of patients. The sublingual dose caused a significant fall in the postoperatively elevated group of patients. The sublingual dose caused a significant fall in the postoperatively elevated plasma glucose, and prevented any further rise in plasma cortisol. 4 Reasons for the efficacy of the sublingual route are discussed and it is suggested that this route may be particularly appropriate for highly lipophilic drugs like buprenorphine.

The permeability of cranial and lumbar dura to various substances including a number of narcotic analgesics was measured in vitro. Preliminary data On human postmortem material is reported. Permeability had a linear relation to the inverse of the square root of molecular weight. This is the expected relationship for a diffusion process dependent upon molecular weight. The differential mass selectivity coefficients for lumbar and cranial dura were calculated; they were similar at 0.8 and 0.9. This was greater than for diffusion in simple liquids, but much less than that for biological lipid membranes. This suggests that the low rates of diffusion are a property of the thickness of the dura rather than any inherent impermeability. A simple model for the dural transfer of drugs is described, and applied to narcotics. Its purposes were to suggest: the factors involved in the dural transfer of drugs; the physicochemical properties of drugs relevant to their dural transfer; worthwhile measurements in future studies. The model indicates that drug molecular weight and rate of absorption are important determinants of the efficiency of dural transfer. Low molecular weight and slow absorption produce high dural transfers. When applied to narcotics, these factors could produce a difference of up to an order of magnitude in the amount transferred directly across the dura.

The plasma concentrations and clinical effects of a single i.v. dose of buprenorphine 0.3 or 0.6 mg were studied in patients recovering from surgery. Analgesic and hormonal effects were greater with the greater dose without a parallel increase in respiratory depression. A comparison with previous work suggests that increased efficacy results either from the use of the larger dose or equivalently if the first required postoperative dose of 0.3 mg has been preceded by a similar loading dose.

Absolute branching ratios for the ␤ decay of 57 Cu to excited states up to 3.3 MeV in 57 Ni have been determined, including the l-forbidden Gamow-Teller transition to the first excited state in 57 Ni. Four transitions to excited states at 0.768, 1.113, 2.443, and 3.007 MeV are observed in addition to the superallowed decay to the ground state of 57 Ni. The measured branching ratio to the ground state is 89.9 Ϯ 0.8% and the branching ratios to the four excited states are 0.94 Ϯ 0.09%, 8.6 Ϯ 0.6%, 0.17 Ϯ 0.03%, and 0.35 Ϯ 0.04%, respectively. In addition we have measured the 57 Cu half-life and find it to be 196.3 Ϯ 0.7 ms, which is in good agreement with the most recent measurement. B͑GT͒ values have been extracted from the new results and are compared to shell model calculations.