Jan l Bernheim medical oncologist reginald Deschepper anthropologist Wim Distelmans palliative care specialist arsène Mullie palliative care specialist Johan Bilsen health scientist luc Deliens medical sociologist, End of Life Care Research Group,

The phannacokinetics of piperacillin were studied in a total of 26 Caucasian normal male volunteers. Single intramuscular doses of 0.5, 1.0, and 2.0 g were given to three groups, each containing eight volunteers. Mean peak serum concentrations of 4.9, 13.3, and 30.2 jig/ml were assayed at 30 to 50 min, and measurable levels were present up to 4, 6, and 8 h, respectively, after dosing. Single intravenous bolus doses of 1.0, 2.0, 4.0, and 6.0 g were given to four groups of five subjects, and mean serum concentrations of 70.7, 199.5, 330.7, and 451.8 ,jg/ml were measured at the end of the injections. The antibiotic had a mean terminal serum half-life of 60 to 80 min after the intramuscular doses and 36 to 63 min after intravenous administrations, depending on the dose. The apparent distribution volume was 20 to 24 liters/1.73 m2, and distribution volume at steady state was 16 to 19 liters/1.73 M2. Mean urinary recovery in 24 h was 74 to 89% for the intravenous doses and 57 to 59% for the intramuscular doses. The piperacillincreatinine clearance ratios indicated that the proportion of renal excretion of piperacillin through tubular secretion was 56 to 73%, and this was confirmed by the renal clearance data from eight volunteers receiving probenecid treatment before the piperacillin dose. Probenecid (1 g given orally before administration of piperacillin) increased peak serum concentration by 30%, terminal serum half-life by 30%, and the area under the plasma concentration curve by 60%, and it decreased the apparent distribution volume by 20% and the renal clearance of the intramuscularly administered (1 g) antibiotic by 40%. Injections of piperacillin by both parenteral routes were well tolerated.Piperacillin (T-1220) is the generic name for sodium 6-[D(-)-a (4-ethyl-2,3-dioxo-1-piperazinylcarbonyl-amino)-a-phenylacetamido] penicillinate, a new semisynthetic aminobenzyl penicillin derivative with an unusually wide spectrum of activity (2,7,9). In vitro testing showed piperacillin to be active against all members of the Enterobacteriaceae, including Klebsiella (of which 58% were inhibited by 8 ,ig/ml), and also against Pseudomonas aeruginosa. The activity of piperacillin was at least equivalent, but generally superior to, that of ampicillin and carbenicillin, especially against Enterobacter species, Klebsiella species, Serratia marcescens, all Proteus species, including the indole-positive species, and Providencia species. Most striking was its activity on P. aeruginosa, of which 50% were inhibited by 2 ,ug/ml and 83% were inhibited by 4 jig/ml (9).Klebsiella pneumoniae, Escherichia coli, P. aeruginosa, Enterobacter species, and, increasingly, S. marcescens are, the major organisms causing life-threatening infections in debilitated patients. The activity of ampicillin is virtually limited to E. coli; that of carbenicillin is extended to Enterobacter species, S. marcescens, and P. aeruginosa, but the majority of the latter species are only inhibited by carbenicillin at concentrations of 32 jug/ml or above. The subs...

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1 Ranitidine single dose pharmacokinetics and absolute bioavailability have been studied in five healthy male volunteers. Following an overnight fast, 150 mg was given intravenously as a bolus injection or orally as a tablet formulation to each subject on separate occasions. 2 Following intravenous administration, plasma levels declined biexponentially. The mean (+ s.d.) distribution half-life (t2¼a) was 6.6 + 1.6 min; plasma half-life (t,12/3) was 1.7 + 0.2 h; the volume of distribution (V) was 96 + 9 1; total body clearance (CL) was 647 + 94 ml/min and renal clearance (CLR) 520 + 123 ml/min. 3 Following oral administration plasma levels showed a bimodal pattern with a first peak at 1.1 + 0.4 h and a second peak at 3 + 0 h. The absolute availability was 60 + 17%. The plasma half-life (t/2) of 2.3 + 0.4 h was significantly longer (P < 0.05) after oral than after i.v. administration. 4 Renal excretion of unchanged ranitidine accounted for 79 + 9% of the dose after i.v. administration and for 27 + 7% after oral administration. 5 Our results suggest a more extensive biotransformation of ranitidine and biliary excretion of metabolites after oral administration while i.v. administered ranitidine is preferentially excreted unchanged in the urine.

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