1 It is well‐known that considerable variability and unpredictability in serum concentrations results from orally administered erythromycin. 2 Disposition kinetics and their variability were studies in 24 healthy subjects after a single dose of erythromycin lactobionate and four doses were studied to evaluate dose‐related variability in five other subjects. 3 Erythromycin kinetics were adequately described by a classical two compartment open model with little intersubject variability. 4 Dose‐related variability occurred. Clearance was independent of dose but T1/2 beta and Vdss increased with dose. 5 Data are presented to show that non‐invasive sampling of urine and saliva are of limited value in studying erythromycin pharmacokinetics.

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Meperidine (ethidine) blood concentrations following multiple intramuscular injections (100 mg) over 2 days were determined in 10 female patients undergoing elective abdominal hysterectomies or cholecystectomies. Pain was estimated by subjective bioassay and the relationship between concentration and effect determined. The blood concentration-effect curve was steep with the range from no analgesia to complete analgesia being 0.35--0.45 microgram/ml on day 1 and 0.4--0.5 microgram/ml on day 2. The mean (+/- S.D.) minimum analgesic blood concentration was 0.5 +/- 0.1 microgram/ml (n = 32). Pain control was poor during the first 4-h dosing interval. The first injection post-surgery was also found to be the least representative of all subsequent injections. Blood concentrations fluctuated in phase with dosing interval, but were highly variable. Intra- and inter-patient peak concentrations varied by 2- and 5-fold and times taken to reach the peaks by 3- and 7-fold, respectively. Hence, meperidine blood concentrations were in excess of the minimum analgesic concentration for only about 35% of each of each 4-h dosing interval. Peak concentrations were not consistently correlated with body weight or lean tissue mass. Variable pain control following intermittent intramuscular meperidine injections was shown to be due to inadequate, fluctuating and unpredictable blood concentrations.