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.

Left ventricular dimensions following training in young and middle-aged men.

To document the effects of endurance training upon left ventricular dimensions, an echocardiographic examination was performed on 11 young (19 +/- 1 years) and 13 middle-aged (40 +/- 3 years) subjects before and after a 20-week endurance training program. The maximal working capacity was increased by 28% and 27% in young and in middle-aged subjects, respectively. Following training, the left ventricular posterior wall and septal thickness in diastole were unchanged both in young (10.1 +/- 0.2 mm and 9.0 +/- 0.2 mm, pre-; 10.1 +/- 0.2 mm and 9.3 +/- 0.3 mm, post-) and in middle-aged subjects (10.0 +/- 0.3 mm and 10.2 +/- 0.3 mm, pre-; 9.7 +/- 0.2 mm and 10.1 +/- 0.2 mm, post-); the left ventricular end-diastolic internal diameter was unchanged in middle-aged subjects (47.8 +/- 0.9 mm, pre-; 48.1 +/- 1.0 mm, post-) but was significantly increased in young subjects (47.8 +/- 1.0 mm, pre-; 49.9 +/- 1.0 mm, post-) (P less than 0.05). These data could suggest that the left ventricular adaptation to training decreases with age. However, the decrease in resting heart rate observed in young subjects (68 +/- 3 to 60 +/- 2 beats X min-1) (P less than 0.05) but not in middle-aged subjects (63 +/- 3 and 65 +/- 3 beats X min-1) could also increase diastolic filling time and explain the small left ventricular end-diastolic enlargement found in the young subjects.

Left ventricular size following endurance, sprint, and strength training.

Left ventricular size following endurance, sprint, and strength training. Med. Sci. Sports Exercise, Vol. 14, No. 5, pp. 344-347, 1982. Left ventricular dimensions in adolescent boys were determined before and after three types of training regimens: endurance (END), N = 8, means = 16.8 yr; sprint (SPR), N = 8, means = 16.3 yr; strength (STR), N = 12, means = 18.7 yr. With training the END group significantly increased VO2max in 1 X min-1 (3.71 +/- 0.27 to 4.16 +/- 0.57, P less than 0.05) and in ml X min-1 X kg-1 (58.4 +/- 5.6 to 64.2 +/- 5.5, P less than 0.05). The SPR group increased VO2max in 1 X min-1 (3.63 +/- 0.63 to 3.98 +/- 0.78, P less than 0.05) but not in ml X min-1 X kg-1 (59.5 +/- 4.1 to 63.2 +/- 5.4) because body weight increased from 61.2 +/- 10.5 to 63.1 +/- 10.7 kg (P less than 0.05) with no change in percent body fat. The STR training group significantly improved upper body strength. Despite these specific training adaptations no significant modifications were found for interventricular and left ventricular posterior wall thickness or for left ventricular internal diameter in either training group. However, calculated left ventricular mass was slightly but significantly higher by 10% and 4% in the END and STR training groups, respectively. These small increases in calculated left ventricular mass with short-term training are probably caused by small but insignificant increases in left ventricular internal diameter secondary to a training bradycardia (END group: 76 +/- 8 to 64 +/- 1 beats X min-1) and to increased diastolic filling time rather than to true cardiac hypertrophy. Significant increases in aerobic capacity and in strength can occur without modification of left ventricular dimensions.

Echocardiography and the Athlete's Heart.

In brief: Echocardiographic studies permit direct, accurate measurements of the ventricular wall thickness and cavity diameter. The authors review several of these studies, which show that elite athletes' left ventricles are larger than those of sedentary persons. Left ventricular wall thickness is greater in athletes excelling in sports involving static exercise, whereas those in endurance sports have larger ventricular cavities. These differences in cardiac dimensions may be the result of genetic makeup, prolonged and strenuous training, or a combination of both. Studies of short-term training showed only minor or no changes in left ventricular morphology, although significant improvements in performance and aerobic capacity were reported.