Misoprostol effects on diclofenac-induced cardiorenal changes in salt-sensitive patients with hypertension: the MEDIC Study.
OBJECTIVE
To determine whether coadministration of misoprostol with the nonsteroidal antiinflammatory drug diclofenac lessens the increase in blood pressure and improves the alterations in renal hemodynamics induced by diclofenac.


METHODS
Prospective, randomized, double-blind, placebo-controlled, crossover study.


METHODS
Two university research centers.


METHODS
Nineteen senior (mean age 62 yrs [range 55-73 yrs]), salt-sensitive patients with stage 1 or 2 hypertension.


METHODS
After a 3-week antihypertensive withdrawal lead-in phase, patients received either diclofenac 75 mg alone or diclofenac 75 mg plus misoprostol 200 microg twice/day for 14 days. After a 10-day washout period, patients received the alternate treatment.


RESULTS
Blood pressure was measured by 24-hour ambulatory blood pressure monitoring, effective renal plasma flow (ERPF) rate was determined by para-aminohippurate clearance, and glomerular filtration rate (GFR) was measured by iothalamate clearance. Mean arterial pressure (MAP = diastolic blood pressure + 0.33[systolic - diastolic blood pressure]) and rate-pressure product (RPP = systolic blood pressure x heart rate x 10(-2)) were also used to compare treatment groups. Diclofenac alone increased MAP by a mean +/- SEM of 5.0 +/- 1.0 mm Hg and RPP by 337 +/- 181 units compared with baseline. The ERPF rate and GFR decreased by 40.5 +/- 26.9 ml/minute and 14.1 +/- 6.5 ml/minute, respectively. Diclofenac plus misoprostol decreased the diclofenac-induced increase in MAP by 3.3 +/- 1.0 mm Hg (95% confidence interval [CI] 1.1-5.3 mm Hg, p=0.004) and decreased the RPP by 724 +/- 238 units (95% CI 225-1223 units, p=0.007). The ERPF rate increased by 56.1 +/- 35.0 ml/minute (95% CI -24.7-137.0 ml/min, p=0.15) and GFR by 18.1 +/- 7.1 ml/minute (95% CI 1.9-34.5 ml/min, p=0.03). Diclofenac alone was relatively well tolerated; no adverse effects were reported with diclofenac plus misoprostol.


CONCLUSIONS
In senior salt-sensitive patients with hypertension, coadministration of misoprostol with diclofenac attenuated the blood pressure elevation and renal vasoconstrictive effects of diclofenac and was well tolerated.
Munger
Mark A
MA
Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, Utah 84112-5820, USA. mmunger@deans.pharm.utah.edu
Gardner
Stephanie F
SF
Ateshkadi
Arasb
A
Rabetoy
Gary M
GM
Barri
Yoursi M
YM
Stoddard
Gregory J
GJ
Cheung
Alfred K
AK
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004008:Diclofenac / Q000009:adverse effects*; D004311:Double-Blind Method; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D016595:Misoprostol / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012965:Sodium Chloride / Q000008:administration & dosage*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016595:Misoprostol; D004008:Diclofenac; D012965:Sodium Chloride