Masahiko Kawabata

Pharmacokinetics of famotidine, a new H2-receptor antagonist, in relation to renal function

SummaryThe pharmacokinetics of a new, potent H2-receptor antagonist, famotidine, 20 mg i.v. was studied in 7 subjects with normal renal function and in 24 patients with varying degrees of renal impairment. The volume of distribution at steady state was 1.14 l/kg in normal subjects and was not altered in renal failure. The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CLCR 90–60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60–30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR below 30 ml/min/1.48 m2). The cumulative urinary excretion and renal clearance of famotidine were correspondingly reduced in patients with impaired kidney function. In normal subjects and in patients with mild to moderate renal failure, about 70% of famotidine was excreted through the kidney, mainly by tubular secretion. In patients with a CLCR above 60 ml/min/1.48 m2 the normal daily dose of famotidine can be employed, but in those with a CLCR between 60 and 30 ml/min/1.48 m2 the dose should be reduced by half, and in patients with a CLCR below 30 ml/min/1.48 m2 a reduction by three quarters of the normal dose is recommended.

Renal Effects Of Efonidipine Hydrochloride, A New Calcium Antagonist, In Spontaneously Hypertensive Rats With Glomerular Injury

1. To obtain some insight into the renoprotective mechanism of the new calcium antagonist efonidipine hydrochloride, we evaluated the acute effects of efonidipine on proteinuria, glomerular haemodynamics and the tubuloglomerular feedback (TGF) mechanism in anaesthetized 24–25‐week‐old spontaneously hypertensive rats (SHR) with glomerular injury.

Combination Therapy with Carvedilol and Nicardipine in Essential Hypertension

Although ,B-blockers and diuretics are widely used first-choice agents in the treatment of hypertension, as recommended in a stepped-care approach (Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure 1984), calcium antagonists have been shown to be effective in most cases of mild to moderate essential hypertension. Patients who do not respond to a calcium antagonist should be treated by adding other drugs, preferably with a different mechanism of action . ,B-Blockers in combination with calcium antagonists have been shown to exhibit synergistic effectsand cause fewer side effects than either agent alone (Anderton et al. 1988; Daniels & Opie 1986). In this study we have evaluated the efficacy and safety of combination treatment with the calcium antagonist nicardipine and a new ,B-blocking agent, carvedilol, in the treatment of mild to moderate essential hypertension. Nicardipine, a calcium antagonist with a dihydropyridine skeleton, is widely used in Japan. Carvedilol is a potent, non-selective ,B-blocking agent with a vasodilating property, and lacks intrinsic sympathomimetic activity (Sponer et al. 1986). 1. Methods 1.1 Patients

The Long Term Effects of Percutaneous Transluminal Angioplasty for Treating Patients with Renovascular Hypertension: Case Studies

Percutaneous transluminal angioplasty was performed on 10 patients with unilateral renovascular hypertension (7 with atheromatous and 3 with fibro muscular stenoses) who were then followed for an average of 42 months (range, 24 to 67 months). Dilatation of the stenosis was initially successful in all patients except one who had severe atheromatous stenosis. Among patients with ather omatous disease, normotension was attained for 40, 25 and 24 months in 3 patients given no antihypertensive medication and for 67 and 55 months in 2 patients given only nicardipine. The remaining one patient had a recurrent stenosis 3 months after angioplasty. All patients with fibromuscular dysplasia have been normotensive without any hypotensive medication for more than 4 years. Plasma renin activity declined within one week after angioplasty and remained unchanged thereafter in all patients except the one case suffering from a recurrent stenosis. Renal blood flow and glomerular filtration rate re mained increased after angioplasty. These results suggest that hypertension can be controlled and renal dysfunction in patients with renal artery stenosis caused by atheroma or fibromuscular dysplasia improved for long periods by percuta neous transluminal angioplasty. The antihypertensive effect obtained by this procedure was more valuable for the patients with fibromuscular dysplasia than in those with atheromatous disease.

A Case of One-Kidney Hypertension: Contrasting Effects of Angioplasty and Treatment with Captopril

A patient with hypertension is shown to have both a renal artery stenosis due to fibromuscular dysplasia and a hypoplastic contralateral kidney, a condition comparable to that of the one-kidney Goldblatt hypertension. Both blood volume and plasma renin activity were increased. Blood pressure was lowered either by an angiotensin II analog or by captopril. Secretion of excess renin was observed only from the stenotic kidney. A 4-week period of captopril treatment was accompanied by an acute, reversible deterioration of renal function. Transluminal angioplasty corrected the abnormalities in renin and in blood volume and has kept blood pressure and renal function normal for over 2 years.