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Publications (3)5.68 Total impact

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    ABSTRACT: The pharmacokinetics of molsidomine were investigated in six young (25.5 +/- 0.6 years) and in six elderly healthy volunteers (81.1 +/- 3.1 years). After a 2 mg oral administration, molsidomine elimination half-life was prolonged in elderly subjects (1.9 +/- 0.2 h versus 1.2 +/- 0.1 h, P less than 0.05) because of a decrease in its plasma clearance (15.1 +/- 3.2 l.h-1 versus 41.8 +/- 2.5 l.h-1 (P less than 0.01) in young volunteers). The elimination half-life of the active metabolite, SIN-1 or linsidomine was also prolonged in elderly subjects (1.8 +/- 0.2 h versus 1.0 +/- 0.08 h, P less than 0.05). AUCs of both molsidomine and SIN-1 were increased in the elderly subjects, but the increase in the former was greater (x 3.4) than the increase in the latter (x 1.6). These results suggest that pharmacokinetics and metabolism of molsidomine are impaired in elderly subjects.
    Fundamental and Clinical Pharmacology 02/1991; 5(6):549-56. · 1.99 Impact Factor
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    ABSTRACT: The pharmacokinetics of a co-trimoxazole preparation (Bactrim Forte) containing trimethoprim (TMP) 160 mg and sulphamethoxazole (SMZ) 800 mg were determined in six young adults (29.3 +/- 4.4 s.d. years) and six elderly people (78.6 +/- 6.6 s.d. years). Following oral administration of a single dose, the pharmacokinetic parameters of SMZ and its N4-acetylated metabolite (N4SMZ) were similar in both groups. However Cmax of TMP was greater (2.06 +/- 0.29 s.d. vs 1.57 +/- 0.32 s.d. mg l-1; P less than 0.01) and its area under the curve was larger (34.30 +/- 6.98 s.d. vs 23.87 +/- 3.82 s.d. mg l-1 h; P less than 0.001) in elderly people than in younger subjects. Total clearance (CL/F) of TMP normalized to body weight was not significantly different in the two groups. There was no significant difference in serum protein binding of TMP and SMZ between the two groups. Urinary excretion of TMP, SMZ and N4SMZ was reduced by about 50% in the elderly compared to the young subjects. Renal clearance of TMP was significantly lower in the elderly group (19 +/- 10 s.d. vs 55 +/- 14 s.d. ml h-1 kg-1; P less than 0.001). Renal clearance of SMZ was not significantly different in the two groups. A study of plasma concentrations of TMP, SMZ and N4SMZ during continuous dosing in seven elderly patients treated for urinary or respiratory infections showed that steady state was reached after 3 days of treatment and that plasma drug concentrations were about two to three times higher than those observed after a single dose.
    British Journal of Clinical Pharmacology 01/1986; 20(6):575-81. · 3.69 Impact Factor
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    ABSTRACT: The pharmacokinetics of Hydergine was studied following intramuscular administration in a group of 6 subjects aged 76-86 and following oral administration in 6 subjects aged 66-86. Comparison with a control group of healthy volunteers (average age of 25) showed: --a marked reduction (- 50%) in renal clearance (p less than 0.001), related to the decrease in creatinine clearance in this population; --a lowering (- 30%) in metabolic clearance (p less than 0.02) in elderly subjects probably related to the decrease in hepatic blood flow observed with age; --a marked increase in bioavailability (X 2.5) following oral administration in elderly subjects, due either to increased absorption, or to a decreased hepatic first-pass effect. These results underline the value of studying the kinetics of geriatric drugs in the target population.
    Journal de pharmacologie 02/1985; 16 Suppl 3:135-43.