Bioavailability Of Buprenorphine Research Articles

Use of GRAS or dietary compounds to improve the oral bioavailability of buprenorphine

Use of GRAS or dietary compounds to improve the oral bioavailability of buprenorphine

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

Background:Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents.Objective:Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets.Methods:Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets.Results:Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant.Discussion:The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space.Conclusion:Drug implants can retain significant and unintended reservoirs of drugs.

Bioavailability of Buprenorphine from Crushed and Whole Buprenorphine (Subutex) Tablets

Background: Buprenorphine (Subutex) is the most abused opioid in Finland. In order to curb the abuse potential of this drug, many treatment centers and prisons crush Subutex tablets before administering them to patients. To date, there are no published studies comparing the efficacy and bioavailability of crushed and whole Subutex tablets. Methods: A total of 16 opioid-dependent patients stabilized on 24 mg of buprenorphine were enrolled in a double-blind, double-dummy, randomized cross-over study comparing crushed and whole buprenorphine tablets on a range of pharmacokinetic and pharmacodynamic variables. Buprenorphine tablets (either crushed or whole) and placebo tablets (either crushed or whole) were administered to subjects simultaneously. Buprenorphine and norbuprenorphine serum levels were measured at 30, 60, 90, 120, 180, 240 and 360 min, as well as 24 h, after tablet administration. After 1 week, the experiment was repeated in a cross-over design so that, by the end of the study, each patient had received the active drug (buprenorphine) as both crushed and whole tablets. Results: Pharmacokinetic parameters (mean serum levels, C_max, T_max, AUC) of buprenorphine or norbuprenorphine did not differ significantly between crushed and whole tablets, although serum levels were slightly higher after administration of the crushed tablets. There were also no significant differences in dissolution/absorption time, withdrawal signs or opiate craving. Conclusion: We conclude that crushing Subutex tablets does not significantly alter serum buprenorphine or norbuprenorphine levels or the drug’s clinical effect. Our results indicate that crushing Subutex tablets may be used as an alternative method to counter the risk of buprenorphine diversion.

Relative bioavailability of different buprenorphine formulations under chronic dosing conditions

Background: Buprenorphine is an approved medication for the treatment of opioid dependence. Three sublingual formulations have been used at various times during its development—a solution containing alcohol, tablets containing buprenorphine alone, and tablets containing buprenorphine plus naloxone. This study compared the relative buprenorphine bioavailability of these different formulations. Methods: Outpatient volunteers ( N=10) were maintained for 14 days of daily administration on each formulation; the dose of buprenorphine (8 mg) was constant across formulations. Blood samples were collected and tested for buprenorphine and norbuprenorphine concentrations after 7 and 14 days maintenance on each formulation. Serial samples were collected before and for 6 h after a daily dose of each formulation. Results: Peak buprenorphine concentrations ( C max) and area under the curve (AUC) for the 6 h interval (AUC 0–6) were highest for the solution and lowest for buprenorphine alone tablets; values for combination tablets were more similar to those for solution. Differences between formulations were less pronounced at day 14 than day 7. There was considerable between-subject variability in concentrations produced. Conclusions: These results suggest there may be greater bioavailability of buprenorphine/naloxone versus buprenorphine alone tablets, and that the bioavailability of buprenorphine from the former is very similar to that seen with solution after 2 weeks of stabilization on each formulation.

Intranasal absorption of buprenorphine — in vivo bioavailability study in sheep

The bioavailability of buprenorphine, HCl (BPP) in sheep after nasal administration of two formulations has been studied. 0.9 mg BPP in 150 μl was administered nasally and compared to 0.6 mg i.v. The test solutions were formulated with 30% polyethylene glycol 300 (PEG 300) and 5% dextrose, respectively. The bioavailability for PEG 300 was 70% (S.D.±27%, n=6), whereas the bioavailability for 5% dextrose was 89% (S.D.±23%, n=6). A two-compartment model with initial and terminal serum half-lives of 10 and 23 min, respectively, may describe the pharmacokinetics. The rate of absorption for both nasal formulations was very fast ( t max=10 min). The C max was 37 ng/ml (S.D.±17) and 48 (S.D.±10) for PEG 300 and dextrose, respectively. No significant difference was found between the two formulations, but PEG 300 has advantages in relation to freezing point depression and solubility, which may be considered if further studies are going to be initiated. The high nasal bioavailability and short time to maximal plasma concentration suggests that it is possible to make a clinically relevant nasal formulation of BPP for the treatment of pain.