Pharmacokinetics of molsidomine and of its active metabolite, SIN-1 (or linsidomine), in the elderly.

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.

[Necrotizing fasciitis and parotitis. Apropos of a case]. / Fasciite nécrosante et parotidite. A propos d'un cas.

A rare lesion, but one particularly serious because of its evolution, necrotizing fasciitis must be treated surgically by wide debridement extending if necessary to the aponeurosis, even if the affection involves the face. A case with combined parotiditis and necrotizing fasciitis is used as a basis for review of the affection.

Pharmacokinetics of the trimethoprim-sulphamethoxazole combination in the elderly.

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.

Hydergine pharmacokinetics in the elderly.

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.

[Double-blind study of Biostim in the prevention of superinfection in patients with chronic bronchopathy]. / Etude en double aveugle du Biostim dans la prévention des surinfections des patiènts atteints de bronchopathie chronique.

In a multicenter trial conducted with patients suffering from chronic bronchopathy, Biostim, an immunomodulating compound of biological origin has been studied using the double-blind placebo-controlled method for prevention of respiratory tract infections. One hundred and ten patients from 10 french pneumology health centers entered the study. The treatment was administered at random in three sequences of 8 days a month for 3 months (2 mg/day the first month, 1 mg/day the second and third months). Patients were separated into 2 groups regarding severity of the disease: group I (non complicated chronic bronchitis); group II (obstructive chronic bronchitis with or without respiratory failure). Patients were examined during 6 months with a monthly appraisal of number, duration and treatment clinically defined infectious episodes. The study of propensity to infections with respect to severity of the disease in patients given placebo showed a significantly lower number of infectious episodes in group I when compared to group II. In the group I (patients suffering from simple chronic bronchitis), no significant difference could be noted between placebo and Biostim but, at all events, the low frequency of episodes makes it difficult to evidence a protective effect in such a group. In contrast, with patients presenting a high infectious risk (group II), one can observe in Biostim treated patients compared with placebo group a significant decrease of infectious episodes and a larger number of patients standing free of episodes throughout the whole period of trial. Tolerance to Biostim has revealed itself satisfactory.

[Comparison of severity and native anti-DNA antibody levels in systemic lupus erythematosus. Serodiscordant lupus]. / Comparaison de la gravité et du taux d'anticorps anti-ADN natif dans le lupus érythémateux disséminé. Les lupus sérodiscordants.

The authors studied the clinicobiological correlations between the severity of systemic lupus erythematosus (SLE) and native anti-DNA antibody levels in 176 patients suffering from this disease. Certain patients were studied at different stages of their disease. This correlation was very close in one out of two cases and relative in one case out of four. In one-fourth of these patients, a significant and persistent discordance existed, and these patients were therefore studied apart. Certain SLE which have been suppressed over long periods of time continue to have elevated anti-DNA levels which are occasionally associated with lowered levels of complement. This has been previously reported in the literature. All decisions to modify corticosteroid treatment based only on biological data is therefore questionable. In contrast, in certain cases of SLE where the evolution of the disease is relatively severe, no anti-DNA or antinuclear antibodies are present. These "seronegative" SLE cases are proof that the "specific" biology of this disease may be erroneous for diagnosis as well as for prognosis. The authors review the possible or known causes for the absence of these antibodies in SLE. They believe that native anti-DNA levels are only of relative value in SLE and feel that these values must be examined with respect to clinical and other biological data in order to treat and survey patients affected with this disease.

[Study of flunitrazepam in the insomnia of the aged (author's transl)]. / Etude du flunitrazépam dans l'insomnie des sujets âgés.

The efficiency of flunitrazepam was evaluated on the three phases of sleep in 20 patients 65 years old and more hospitalized suffering from severe insomnia. The experiment lasted 6 days. The initial dosage of half a tablet was sufficient and was maintained in 13 patients. In 5 subjects, dosage had to be increased to one tablet. In one subject, it was reduced to a quarter of a tablet. In the three quarters of the patients, the onset of sleep was of better quality; their actual sleep was longer and also of higher quality. The waking up was much easier in 18 patients who felt relaxed and alert during the morning. The alertness tests confirmed the patients state. The efficiency was satisfactory and the tolerance was very good. Taking into account the individual sensitivity of the aged, initial dosages must be small and adjusted according to the therapeutic responses.