Nordic Walking may improve exercise capacity, lower body endurance and coordination of movements in patients with good exercise tolerance participating in early, short-term rehabilitation after an acute coronary syndrome.
The dose-dependence of the nifedipine-digoxin interaction was investigated in seven healthy subjects. After an adequate loading dose of digoxin for 2 weeks, 0.25 mg digoxin b.i.d. was given by mouth by itself. Afterwards, 0.25 mg digoxin was given twice a day for three 1-week periods in combination with capsules of nifedipine, 5, 10, or 20 mg, respectively, given on a thrice-daily basis. The study ended with a digoxin monotherapy phase lasting 7 days. All three doses of nifedipine significantly increased digoxin plasma concentrations and AUC compared with digoxin monotherapy. Thus, for example, the AUC was 10.16 +/- 0.88 ng/ml . hr (mean +/- SE) when digoxin was given alone and 12.33 +/- 1.59 ng/ml . hr with concurrent nifedipine, 5 mg t.i.d. (P less than 0.05). Nifedipine causes a slight but significant increase (15%) in digoxin plasma concentrations and AUC. This effect did not depend on the nifedipine dose given in the range studied.
The elimination of diazepam and antipyrine and the urinary excretion of their metabolites were investigated in 21 healthy volunteers before and after 7 days of administration of antipyrine, 1200 mg, and rifampin, 600 or 1200 mg. After administration of antipyrine and rifampin in two doses, antipyrine total body clearance increased by 53% and 60% or 98%, respectively. The clearance to metabolite showed a preferential induction of the norantipyrine pathway with different proportions after antipyrine and rifampin; rifampin, 1200 mg, also enhanced the 4-hydroxyantipyrine pathway further. After antipyrine, diazepam total body clearance was increased by 102%, affecting all metabolic pathways to a similar extent. After rifampin in both doses, diazepam total body clearance rose equally to 300% and desmethyl- and 3-hydroxydiazepam metabolic clearance to 400%. Therefore rifampin preferentially affects norantipyrine or desmethyl- and 3-hydroxydiazepam metabolic formation, suggesting induction of different (iso)zymes of cytochrome P-450.
Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwards nitrendipine 20 mg once daily were administered orally for seven days. With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0-24), was 94.5 ng ml-1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0-24) h was significantly greater at 309.4 ng ml-1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance. Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.
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