In an open-label, randomized, crossover study 12 healthy volunteers were given clarithromycin orally 250 mg twice daily (b.i.d.) and 500 mg once a day (q.d.). Blood and saliva samples were collected on study days 1 and 5 to determine the pharmacokinetics of clarithromycin and its 14-hydroxy metabolite in plasma and saliva, and to measure concentrations of clarithromycin in mononuclear cells (MNCs) and polymorphonuclear leucocytes (PMNs). The mean peak levels of clarithromycin on day 5 of therapy in serum (2.3 vs. 1.2 mg/l), saliva (1.1 vs. 0.3 mg/l) and blood cells 60 vs. 26 mg/l in MNCs and 29 vs. 14 mg/l in PMNs) were at least doubled, the trough levels were lower with 500 mg q.d. vs. 250 mg b.i.d. (0.09 vs. 0.28 mg/l in serum; 0.06 vs. 0.13 mg/l in saliva; < 1 vs. 6.8 mg/l in MNCs; 0.8 vs. 2.8 mg/l in PMNs). The mean relative peak serum concentrations of the 14-hydroxy metabolite were somewhat lower with the 500 mg dosage (0.78 vs. 0.46 mg/l). The peak concentrations of clarithromycin and its 14-hydroxy metabolite in saliva were 25-40% and 50-80% of the maximum serum concentrations with both dosage regimens. Clarithromycin exhibits good and rapid penetration into intracellular as well as into extravasal extracellular body compartments. Clarithromycin 500 mg q.d. compares favourably with 250 mg b.i.d., as far as peak serum levels and bioavailability are concerned, but trough levels are lower at the end of the 24-hour dosing interval.

Administration, Oral↗

PubMedDate not supplied

Circulating and tissue catecholamines in rats with chronic neurogenic hypertension.

To study the role of peripheral catecholamines in plasma and different tissues in neurogenic hypertension we measured directly blood pressure, maximum rate of left ventricular pressure rise (dp/dtmax) and heart rate through an aortic catheter 5 weeks after total sino-aortic baroreceptor deafferentation in male Sprague-Dawley rats. Blood samples were collected through the same catheter to determine plasma catecholamine concentrations. Blood pressure and dp/dtmax were significantly higher in neurogenic-hypertensive rats when compared with sham operated rats. Plasma noradrenaline concentrations and plasma adrenaline concentrations reached significantly higher levels in neurogenic-hypertensive rats. In the heart noradrenaline content was lower (when calculated per g wet weight) and in the adrenal medulla adrenaline content was higher in neurogenic-hypertensive rats, when compared with sham operated controls. A significant positive correlation was found between dp/dtmax and plasma noradrenaline concentrations. It is concluded that sino-aortic baroreceptor deafferentation produces a significant chronic hypertension, probably supported by elevated plasma catecholamine concentrations and enhanced synthesis and release of adrenaline from adrenal medulla.

Adrenal Glands↗

PubMedDate not supplied

Membrane effects of drugs interfering with adrenergic mechanisms.

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1-Propanol↗