Effect of Metamizole (Dipyrone) on Renal Function in Salt-depleted Healthy Subjects
Status:
Completed
Trial end date:
2014-04-01
Target enrollment:
Participant gender:
Summary
The planned study is a single-center, randomized, open-label parallel group study in 16
healthy male subjects. Study subjects will be randomly allocated either to the metamizole
group (1) or to the naproxen group (2). All participants will start with a low sodium diet
(approximately 50 mmol Na+ per day) 7 days before the first drug intake and maintain the diet
until the end of the study (14 days in total). Salt-depletion is an accepted model to enhance
production of vasodilatory prostaglandins and to increase renal sensitivity to prostaglandin
inhibition. On the first day of treatment (Day 1), a single dose of metamizole or naproxen
will be administered to investigate the effects after a single dose and to collect single
dose pharmacokinetic profiles. Starting on Day 2, all participants will receive therapeutic
doses, i.e. 1000 mg metamizole 'ter in die' (TID, three times a day) or 500 mg naproxen 'bis
in die' (BID, twice a day) for one week and on Day 7 pharmacokinetics and pharmacodynamics
effects will be assessed under near steady-state conditions.
The primary objective is the characterization of the renal effects of metamizole by
determination of the glomerular filtration rate (GFR) using the inulin clearance. Secondary
objectives are the characterization of the urinary excretion of prostaglandin E2 (PGE2) and
the prostaglandin I2 (PGI2) metabolite 6-keto-prostaglandin F1 (PGF1)alpha as well as the
urinary excretion of sodium and potassium.
Overall, clinical experience suggests better renal tolerability of metamizole possibly due to
less potent COX-inhibition compared to classical nonsteroidal antiinflammatory drugs
(NSAIDs). If this could be confirmed, metamizole would be a valuable alternative for
treatment of painful conditions in patients with impaired renal function. Therefore, the aim
of this study is to examine the effects of metamizole on renal function in comparison with
the non-specific COX-inhibitor naproxen.