Pentazocine pharmacokinetics

All clinically used opiates have the same pharmacology since they all act on the mu receptor with the exception of the kappa agonist, pentazocine. Opiates are used to relieve moderate to severe pain whatever the cause (accidents, post-operative pain, cancer, etc.) and are used pre-, intra- and post-operatively. The mu opiates differ only in potency and pharmacokinetics. Examples are ... 

Pharmacokinetics Pentazocine is well absorbed from the Gl tract and from subcutaneous and IM sites. Oral bioavailability is less than 20% concentrations in plasma coincide closely with onset, intensity and duration of analgesia. It is excreted via the kidney, less than 5% unchanged. 

Pharmacokinetic properties Pentazocine is orally bioavailable but there is a high degree of fluctuation in resorption. The compound is rapidly and extensively metabolized. Metabolites are formed by oxidative demethylation of the methyl residues of the dimethylallyl group and by glucuronidation (Berkowitz, 1973). The metabolic pathway of pentazocine is shown in scheme 42. 

Berkowitz, B. Pharmacokinetics and neurochemical effects of pentazocine and its optical isomers, Adv. Biochem. Psychopharmacol. 1973, 8, 495-501. 

Way and coworkers. Reviews of metabolism (51) and pharmacokinetics (97) of pentazocine have been published. The effect of route of administration on the disposition of pentazocine has been explored (27, 9,75,85,86). The metabolic pathways available to pentazocine are outlined in Figure 10. Also shown are urinary excretion data for the metabolites expressed as percent of administered dose. 

The pharmacokinetics of pentazocine have been investigated in humans (11,76,86). Table 13 shows values for half-life, volume of distribution, bioavailability and clearance calculated by various authors. The plasma half-life values obtained range from 2 to 5.7 hours. The possibility that... 

Studies of pentazocine biological disposition in animals consist of tissue uptake (26,52,58,65, 68,79), blood level (50,61,7 0 and urine level determinations (88). While animal metabolic pathways identified (39. 0,70) are similar to those found in man, additional products have been demonstrated. In the rat 9-methoxypentazocine (or its 8-methoxy-9-hydroxy isomer), 8,9 (or 9.8)-methoxy-hydroxy metabolite of the cis-alcohol product and 8,9 (or 9,8)-methoxyhydroxy metabolite of the transalcohol product were found. Pharmacokinetic studies have been done in rhesus monkey (66) and in the dog (35t5 63) Typical plasma half-lives measured in dog plasma are 1.2-1.6 hours. A day-night variation was also observed in the calculated parameters (35). 

Pharmacokinetics. Pentazocine is extensively metabolised in the liver and less than 10% is excreted unchanged in the urine (P/ 5 h). 

A number of drugs of abuse are known substrates (e.g., codeine, hydrocodone, p-methoxyamphetamine, amphetamine) or inhibitors (e g., (-)-cocaine, pentazocine) of CYP2D6. For some of these drugs, the pharmacokinetic differences due to the polymorphism will be so profound that they are likely to exceed pharmacodynamic sources of variation in response. For other drugs (e.g., hydrocodone to hydromorphone, codeine to morphine, oxycodone to oxymorphone), CYP2D6 may not contribute importantly to the overall clearance of the drug, but may catalyze the formation of highly active metabolites. 

Diamorphine, morphine, oxycodone, pentazocine and pethidine delay gastric emptying so that the rate of absorption of paracetamol given orally is reduced. There is no pharmacokinetic interaction between codeine and paracetamol, but the combination may not always result in increased analgesia. 

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