Pharmacokinetics buprenorphine

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

Butorphanol, an analog of buprenorphine, showed a nasal bioavailability of 70% and also a much lower Tmax after nasal absorption as compared with the sublingual and buccal routes [115]. Lindhardt et al. [106] compared buprenorphine formulated in 30% PEG-300 in sheep with that of the 5% dextrose formulation mentioned earlier. A unit-dose Pfeiffer device was again used to administer the formulation. It was found that nasal bioavailability in sheep was about 70% when buprenorphine was formulated in PEG-300 and approximately 89% when it was formulated with 5% dextrose. The rate of absorption was reported to be very fast, with a Tmax of 10 min the Cmax was found to be 37 and 48ng/mL for PEG-300 and dextrose, respectively. In sheep, the pharmacokinetics of buprenorphine showed a two-compartment model as compared to a three-compartment model in humans. 

OPIOIDS ANTIFUNGALS 1, Ketoconazole T effect of buprenorphine 2. Fluconazole and itraconazole T the effect of alfentanil 3. Fluconazole and possibly voriconazole T effect of methadone this is a recognized pharmacokinetic effect but of uncertain clinical significance 1. Ketoconazole 1 the CYP3A4-mediated metabolism of buprenorphine 2.1 clearance of alfentanil 3.1 hepatic metabolism 1. The dose of buprenorphine needs to be 1 (by up to 50%) 2. i dose of alfentanil 3. Watch for T effects of methadone... 

Yassen, A. et al., Animal-to-human extrapolation of the pharmacokinetic and pharmacodynamic properties of buprenorphine, Clin. Pharmacokinet., 46(5), 433, 2007. 

Ho, S.-T. Wang, J.-J. Ho, W. Hu, O.Y.-P. Determination of buprenorphine by high-performance liquid chromatography with fluorescence detection application to human and rabbit pharmacokinetic studies. J.Chromatogn, 1991, 570, 339—350... 

Garrett ER and Ravi Chandran V, Pharmacokinetics of morphine and its surrogates. Part 6. Bioanalysis, solvolysis kinetics, solubility, pK a values and protein binding of buprenorphine, /. Pharm. ScL, 74, 515-524 (1985). 

Sudden deaths in patients who abuse opioids are frequently associated with ingestion of other CNS depressants, particularly benzodiazepines. Cases have been reported with buprenorphine, oxycodone, and tramadoF taken with various benzodiazepines. It has not been established exactly why this occurs, but both pharmacodynamic and pharmacokinetic mechanisms are possible. The deleterious interaction of benzodiazepines and opioids on respiration is possibly due to central effects and/or additive actions on the different neuromuscular components of respiration. For buprenorphine, it is considered most likely that ex-... 

EUcader A, Sproule B. Buprenorphine clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokimt (2005) 44, 661-80. 

The clearance of morphine is roughly doubled by combined oral contraceptives. Combined oral contraceptives do not appear to alter the pharmacokinetics of pethidine. The manufacturer of bu-prenorphine predicts that gestodene may increase plasma levels of buprenorphine. 

Peginterferon alfa does not affect the pharmacokinetics of methadone, but an isolated report describes a patient who relapsed to heroin use following treatment with peginterferon. Methadone maintenance does not appear to affect the pharmacokinetics of peginterferon alfa or the virological response to interferons. Similarly, buprenorphine does not appear to influence the effect of interferon. 

Buprenorphine. In one study, there was no difference in the pharmacokinetics of oral zidovudine between patients receiving buprenorphine and control subjects. Buprenorphine is not expected to cause zidovudine toxicity. 

Preliminaiy evidence suggests that buprenorphine does not affect the antiretrovirai efficacy or pharmacokinetics of delavirdine and efavirenz. Deiavirdine may increase buprenorphine plasma levels and efavirenz may decrease buprenorphine levels, but the clinical significance has not been fully investigated. Delavirdine given with buprenorphine/naloxone has been shown to slightly prolong the QT interval. 

Bruce RD, Altice FL. Three case reports of a clinical pharmacokinetic interaction with buprenorphine and atazanavir plus ritonavir. AIDS (2006) 20, 783-4. 

BuUingham R, McQuay H, Dwyer D, Allen M, Moore R. Sublingual buprenorphine used post-operatively clinical observations and preliminary pharmacokinetic analysis. BrJClin Pharmacol 1981 12(2) 117-122. 

KapU RP, Cipriano A, Michels GH, Perrino P, O Keefe SA, Shet MS, et al. Effect of ketoconazole on the pharmacokinetic profile of buprenorphine following adininistration of a once-weekly buprenorphine transdermal system. Clin Drug Invest September 1,2012 32(9) 583-92. 

Douglas Bruce R, Moody DE, Chodkowski D, Andrews L, Fang WB, Morrison J, et al. Pharmacokinetic interactions between buprenor-phine/naloxone and raltegravir in subjects receiving chronic buprenorphine/naloxone treatment. Am J Drug Alcohol Abuse 2013 39(2) 80-5. 

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