Bioavailability and first‐pass metabolism of oral pentazocine in man

Ehrnebo, M.; Boréus, L. O.; Lönroth, Ulla

doi:10.1002/cpt1977226888

Cited by 62 publications

(20 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No information is available from long term studies. The studies by Ehrnebro et al (1977) and Neal et al (1979) used fluorescence and gas liquid chromatography with electron capture detection, respectively, and the agreement between the results is striking. Both studies used venous samples and both analysed individual intravenous patient data by biexponential fitting.…”

Section: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 55%

“…In the oral studies, Ehrnebro et al (1977) used a dose of loomg (2 )( 50mg tablets) while Neal et al (1979) used 0.4 mg/kg in solution. The measured oral bioavailability was 18% in both studies and close to the value predicted from the intravenous pharmacokinetics .…”

Section: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 99%

“…Both studies used venous samples and both analysed individual intravenous patient data by biexponential fitting. Ehrnebro et al (1977) used a 30mg intravenous dose; the study lasted for 6 hours, but had few early sample points. Neal et al (1979) used an intravenous dose of 0.4 mg/kg; they sampled for 10 hours, but did not quote an exact sampling schedule.…”

Section: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 99%

See 2 more Smart Citations

Clinical Pharmacokinetics of Narcotic Agonist-Antagonist Drugs

Bullingham

McQuay

Moore

1983

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Narcotic agonist-antagonist drugs are able specifically to reverse the effects of morphine and other opiate agonists in some pharmacological preparations. They also have some agonist properties which in some cases may be extensive and provide useful clinical properties such as analgesia, or may be minimal. Thus pentazocine, buprenorphine, nalbuphine and butorphanol all demonstrate definite analgesic properties. Naltrexone, in contrast, has only limited agonist action, as shown for example in pupil constriction, and is perhaps better regarded as an antagonist.After intravenous administration of buprenorphine there is an initially rapid early distribution phase with a half-life of about 2 minutes. Studies on butorphanol and pentazocine had insufficient early samples to allow accurate analysis of this phase. Otherwise, the intravenous pharmacokinetics for ali these drugs show bi-or tri-exponential decay with terminal half-lives of between 3 and 5 hours, plasma clearances of between 1200 and 2800 ml/min, and apparent volumes of distribution of 200 to 400L. These values for plasma clearance and terminal ha(f-l!fe have been confirmed in oral and intramuscular studies.There is only limited information about the rate or extent of absorption after intramuscular administration. For buprenorphine peak plasma concentrations are reached between 2 and 5 minutes; for pentazocine and butorphanol the peak is later, at between 15 and 60 minutes for pentazocine and 45 minutes for butorphanol. Systemic availability of intramuscular buprenorphine is in the range of 40 to 100%, but is generally greater than 90%. Availability of intramuscular butorphanol has been reported to be complete.Oral systemic availability for drugs with a high plasma clearance is predictably low because of a significant first-pass effect through the liver. The oral availabilities of pentazocine and nalbuphine have been calculated to be about 20%, and although there are no pharmacokinetic data, some evidence of clinical efficacy suggests a similar figure for butorphanol and buprenorphine. For naltrexone however, the available data suggest that this drug is completely absorbed after oral administration.Only buprenorphine has been studied by the sublingual route. The systemic availability was variable (16 to 94%), but on average it was 55% in a study of long duration; the absorption half-life from the buccal cavity was estimated to be 76 minutes. Over a limited dose range there appeared to be linear increases in the maximum rise in plasma concentration and A UC with buprenorphine administered by this route. There have been no pharmacokinetic studies of the narcotic agonist-antagonist drugs by other routes of administration, such as after intrathecal or extradural administration, or rectally or transcutaneously.Pharmacodynamic data for these drugs are incomplete. AnalgeSia in man appears to be dose-related for pentazocine, butorphanol, buprenorphine and nalbuphine; morphine antagonism is dose-related for naltrexone. The appearance of opiate side effects (nausea and...

show abstract

Section: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 55%

Section: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 99%

Section: Fundamental Pharmacokinetic Propertiesmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Pharmacokinetics of Narcotic Agonist-Antagonist Drugs

Bullingham

McQuay

Moore

1983

Clinical Pharmacokinetics

View full text Add to dashboard Cite

show abstract

“…The re- Table 11). The two-compartment model was used recently to describe pentazocine pharmacokinetics in healthy humans (18) where the average terminal disposition half-life was 209 min.…”

Section: Results a N D Discussionmentioning

confidence: 99%

Plasma pentazocine radioimmunoassay

Peterson

Graham

Banks

et al. 1979

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…Ehrnebo et al (19) and studies conducted in our laboratories" have demonstrated that first-pass metabolism of pentazocine after oral administration was -80%. Taking this into account, one obtains mean estimates of 222 and 322 L for the tablet and solution treatments, which are in reasonable agreement with the range of 251-548 L reported by Ehrnebo et al (19) (19,21 been observed that the AUC values vary substantially for drugs with pronounced hepatic clearance, such as nortriptyline (23) and imipramine (24); the data suggest this is also true for pentazocine. In addition, the oral bioavailability of pentazocine was significantly enhanced in patients with cirrhosis of the liver, due to reduction in hepatic clearance (20,…”

mentioning

confidence: 96%