The pharmacokinetics and tolerability of two dosage forms for rectal administration of paracetamol were compared. A fatty suppository was compared with a solution of 60 mg/ml paracetamol. Both dosage forms were given as 1000 mg doses to 10 healthy adult volunteers. The solution produced peak plasma concentrations significantly faster (t (max)) than did the suppository. The peak concentration (C(max)) and the area under the curve (AUC(6)) were also significantly greater. The pharmacokinetic characteristics of the solution were superior to those of the suppository. No difference in irritation score was identified and no discomfort was reported.

Propylene glycol is an excipient of various pharmaceutical preparations. The pharmacokinetics after rectal administration are studied, followed by a consideration on local and systemic side-effects for a solution of paracetamol in a mixture of propylene glycol and water. After administration of 8.64 g propylene glycol to 10 adults and 173 mg/kg body weight to 4 children, peak concentrations (Cmax) of 199 mg/l and 171 mg/l respectively were reached (tmax) after 1.5 hr and 1.0 hr. The average terminal half-lives (t1/2) in adults and children were respectively 2.8 hr and 2.6 hr, total body clearance (CI/F) 0.20 l/hr*kg and 0.21 l/h*kg and apparent volume of distribution (VD/F) 0.79 l/kg and 0.77 l/kg.

An exploratory study in paediatric surgical patients was performed to describe the behaviour of a rectal solution of paracetamol at 20 mg/kg. Four of six patients were able to complete the study. Peak concentration (Cmax) and time to peak concentration (tmax) found in the children are comparable to adults studied earlier. After 1.6 hrs (tmax) a peak concentration of 11.7 mg/l (Cmax) was reached. The area under the curve (AUC t = 6) and the mean residence time (MRT) were respectively 48.3 mghr/l and 5.2 hrs. The solution appears promising for further study in daily clinical practise.

A rapid high-resolution high pressure liquid chromatographic method was developed for assaying pilocarpine. Pilocarpine in ophthalmic solutions decomposes fairly rapidly to give isopilocarpine, pilocarpic acid and isopilocarpic acid. The quality of an ophthalmic solution can be assessed by assaying these decomposition products. Existing high pressure liquid chromatographic methods suffer from long analysis times and poor resolution. The new method uses as the mobile phase 6 ml/l of triethylamine in water (pH 2.3, adjusted with 85% phosphoric acid) at a flow of 1.5 ml/min and as the stationary phase a C18-silica 125 x 4.6 mm column. 2-Amino-1-phenyl-1,3-propanediol is used as an internal standard. Complete separation was obtained within 8 min. Pilocarpine eye drops were stored under different conditions and then analysed for decomposition products. During heat treatment, decomposition to isopilocarpine predominated over decomposition to pilocarpic or isopilocarpic acid. However, when stored at room temperature or in a refrigerator, formation of pilocarpic acid clearly prevailed. Thus, from assessment of decomposition products, the cause of decomposition can be established.

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