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J L Chalmers

Publications and source records attributed to J L Chalmers.

4 recordsLinked to original sources

Analysis of meperidine and normeperidine in serum and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the simultaneous analysis of meperidine and normeperidine in serum and urine. A 1-ml sample aliquot is extracted into hexane, then back-extracted into a small volume of dilute acid which is injected onto a cyanopropyl analytical column. Absorbance of the column effluent is monitored at 205 nm. Two internal standards are employed, diphenhydramine for meperidine and nordiphenhydramine for normeperidine. Chromatography of the four compounds takes 4 min. Serum concentration--time curves of meperidine and normeperidine are presented for eight healthy subjects following single 70-mg bolus injections of meperidine.

Adult↗

Ranitidine does not alter pethidine disposition in man.

The effect of concurrent ranitidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (19-33 years). The subjects received 70 mg i.v. pethidine HCl doses before and during ranitidine treatment (150 mg p.o. twice daily). Ranitidine therapy was not associated with significant alterations in pethidine elimination rate constant, volume of distribution at steady state, total body clearance, and 24 h urinary excretion. No alteration in pethidine oxidation to norpethidine was noted, as suggested by nonsignificant changes in lag time to appearance of quantifiable norpethidine in serum, time to peak concentration, peak concentration, area under the curve from time 0.24 h, and 24 h urinary excretion. It would appear that, unlike cimetidine, ranitidine does not interact pharmacokinetically with pethidine. Further studies are necessary to evaluate the potential clinical advantages of ranitidine vs cimetidine therapy in patients also receiving pethidine.

Adult↗

Cimetidine alters pethidine disposition in man.

The effect of concurrent cimetidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (18-31 years). The subjects received 70 mg i.v. pethidine HCl doses before and during cimetidine treatment (1200 mg/day p.o.). During cimetidine treatment, pethidine total body clearance (CL) decreased by 22% (0.611 +/- 0.101 [mean +/- s.d.] to 0.474 +/- 0.098 1 kg-1 h, P less than 0.05) and pethidine volume of distribution at steady state (Vss) decreased by 13% (4.79 +/- 0.82 to 4.16 +/- 0.75 l/kg, P less than 0.05). A cimetidine-induced reduction in pethidine oxidation to norpethidine was suggested by a 23% reduction in norpethidine area under the curve from 0 to 24 h (472 +/- 93 to 362 +/- 38 ng ml-1 h, P less than 0.05) and a 29% reduction in peak norpethidine concentration (26.7 +/- 5.3 to 18.9 +/- 1.9 ng/ml, P less than 0.05). There were no significant linear correlations of serum trough cimetidine concentration with percentage reductions in pethidine CL, pethidine Vss, norpethidine AUC (24), or norpethidine peak concentrations. It would appear that the cimetidine-pethidine kinetic interaction may be of sufficient magnitude to be clinically significant. Caution is advised when patients are treated concurrently with these two agents.

Adolescent↗

A fatal overdose with clomipramine.

A death attributed to self administration of toxic amounts of clomipramine is reported. Analysis of post mortem blood showed clomipramine at a concentration of 540 ng/mL and its active metabolite, N-desmethylclomipramine, at a concentration of 580 ng/mL. The corresponding concentrations of the parent compound and metabolite in the urine were only 350 ng/mL and 700 ng/mL, respectively. These blood results are construed to represent minimum lethal concentrations for the two combined compounds.

Chromatography, Gas↗