Analysis of the natriuretic action of a loop diuretic, piretanide, in man.

Abstract

1 The renal responses to a loop diuretic, piretanide, were investigated in a group of fourteen healthy volunteers. The effect of fluid replacement on the drug-response relationship was evaluated in the absence and in the presence of probenecid pretreatment following both oral and intravenous administration of piretanide. 2 Urinary excretion of piretanide was greater when volume losses were replaced than in the absence of volume replacement (i.v. dose: 3.32 ± 0.15 vs 2.55 ± 0.23 mg 6 h-1, P < 0.01; oral dose: 2.57 ± 0.09 vs 1.87 ± 0.27 mg 6 h-1, P < 0.01). With intravenous piretanide urinary excretion of sodium was likewise greater in the fluid replaced group (198 ± 4 vs 141 ± 10 mmol 6 h-1, P < 0.01); these differences caused by fluid replacement did not however occur after oral dosing of piretanide (181 ± 12 vs 167 ± 14 mmol 6 h-1).

Discrepancy between bioavailability as estimated from urinary recovery of frusemide and total diuretic effect.

“…formulations still give not much less response although the fraction absorbed is about 50% lower. The efficiency concept was recently criticised by Noormohamed (1990) and Noormohamed & Lant (1991). Given that the Hill equation adequately models the diuretic effect, the efficiency is a simple mathematical consequence (Alvain et al, 1991).…”

“…Given that the Hill equation adequately models the diuretic effect, the efficiency is a simple mathematical consequence (Alvain et al, 1991). In a recent paper, Noormohamed & Lant (1991) have chosen to display their data only as cumulative excretion of sodium vs cumulative excretion of the loop diuretic piretanide. Displaying the data in this way will however disregard the pharmacodynamic relationship expressed e.g.…”

Muzolimine: Renal site of action and interaction with probenecid in humans

“…35 An alternative explanation, put forward by us recently, is that there are fundamental differences in the mechanics of the response when a diuretic is administered intravenously as a bolus dose as opposed to the effect of sustained intravenous infusion or an oral dose. 36 The nephron may be refractory to the initial delivery of the diuretic while retaining appropriate sensitivity to all subsequent delivery of the drug. Thus after intravenous dosing of the loop diuretic piretanide, an average of 17% of the total amount of drug excreted over a period of 6 hours was delivered to the kidney during an early phase when no saluretic response occurred.…”

“…Thus after intravenous dosing of the loop diuretic piretanide, an average of 17% of the total amount of drug excreted over a period of 6 hours was delivered to the kidney during an early phase when no saluretic response occurred. 36 No such refractory phase was VOLUME 50 NUMBER 5, PART 1 Site of diu~etic action of vvluzolirnine 5 7 1 observed after oral administration of the loop diuretic alone or with probenecid pretreatment. 36 In conclusion, this study confirms that the renal site of action of muzolimine in humans is located primarily in the medullary portion of the TAL.…”

“…36 No such refractory phase was VOLUME 50 NUMBER 5, PART 1 Site of diu~etic action of vvluzolirnine 5 7 1 observed after oral administration of the loop diuretic alone or with probenecid pretreatment. 36 In conclusion, this study confirms that the renal site of action of muzolimine in humans is located primarily in the medullary portion of the TAL. Muzolimine also has additional inhibitory actions on proximal tubular transport processes.…”