Pethidine pharmacokinetics

Cimetidine 600 mg twice daily for one week reduced the total hody clearance of a single 70-mg intravenous dose of pethidine in 8 healthy subjects by a modest 22%." In a similar study by the same research group, ranitidine 150 mg twice daily had no effect on pethidine pharmacokinetics. ... 

Pharmacokinetic properties Pethidine (Mather and Meffin, 1978) has a faster onset and a shorter duration of action than morphine. After oral administration about 50% of the drug is eliminated by first-pass metabolism. N-demethylation yields the active metabolite nor-pethidine, and hydrolytic cleavage the inactive metabolites pethidinic and nor-pethidinic acid. The half-life of pethidine is about 3- 6 h. Nor-pethidine has a much slower elimination with a half life of up to 20 h. 

This chapter concentrates on some drug choices in acute rather than chronic pain, but the same principles can be used to determine the appropriateness of other types of analgesic. The drugs considered in this section are paracetamol, non-steroidal anti-inflammatories (NSAIDs specifically diclofenac, ibuprofen, indometacin, naproxen, sulindac and tenoxicam) and opioids (codeine, dihydrocodeine, morphine, pethidine and tramadol). Unless otherwise stated, all pharmacokinetic data originate from standard reference sources [1-5] and apply to adults only. 

GC-MS methods provide greater specificity and in many cases sensitivity when compared with more conventional techniques. They offer increased scope for the study of pharmacokinetics and of plasma concentration in relation to biological effect. SIM assay has been applied to the investigation of placental transfer of lipid soluble drugs and their subsequent elimination in the newborn (barbiturates, diphenylhydantoin, caffeine, pethidine and diazepam [122,408] diphenylhydantoin [411] amylobarbitone and 3 -hydroxyamylobarbitone [83,423]). 

The pharmacokinetics and effects of various systemically administered analgesics on the uterus, fetus, and neonate have been reviewed (SED-11, 137). Fetal bradycardia lasting up to 7 minutes was reported in 53 of 1910 fetuses (2.7%) after the administration of pethidine (meperidine) 75 mg and promethazine 25 mg intravenously to the mothers during labor (SED-11,137) (95). 

Remifentanil by infnsion (n = 49) has been compared with titrated bolnses of pethidine (n = 51) in a randomized, donble-blind stndy in 100 patients undergoing outpatient colonoscopy (9). The incidences of tachycardia, hypotension, and nausea were significantly less with remifentanil than with pethidine, but there were higher anxiety and pain scores with remifentanil. However, the study was a comparison of two opioids with different pharmacokinetic profiles, which makes it very difficult to achieve equipotent doses for the purpose of comparison. 

Wan P Y, Trim C M, Mueller P O 1992 Xylazine-ketamine and detomidine-tiletamine-zolazepam anesthesia in horses. Veterinary Surgery 21 312-318 Waterman A E, Amin A 1992 The influence of surgery and anaesthesia on the pharmacokinetics of pethidine in the horse. Equine Veterinary Journai Suppiement 11 56-58 Waterman A E, Robertson S A, Lane J G 1987 Pharmacokinetics of intravenously administered ketamine in the horse. Research in Veterinary Science 42 162-166... 

Information about the interaction between pethidine and cimetidine is very limited, and its clinical importance is uncertain, but probably small given the minor changes in pharmacokinetics. However, some manufacturers warn that cimetidine may inhibit the metabolism of pethidine and thus caution should be used with concurrent use. Ranitidine has been shown not to affect the pharmacokinetics of pethidine. 

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. 

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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