Effect of oral administration of losartan, prazosin, and verapamil on peritoneal solute transport in continuous ambulatory peritoneal dialysis patients.
BACKGROUND
Several intraperitoneally administered drugs have been shown to modify transport of peritoneal solute and fluid. Fewer studies, however, have evaluated the effect of orally administered drugs. The present study was performed to evaluate the effects of oral losartan, prazosin, and verapamil on peritoneal membrane transport during a peritoneal equilibration test (PET), as well as the effects on creatinine clearance (CrCl), Kt/V urea, 24-hour protein in drained dialysate, and drained volume.


METHODS
This was an open, controlled, crossover clinical trial performed in 20 patients on continuous ambulatory peritoneal dialysis. All subjects used four 2-L 1.5% glucose dialysis exchanges per day. After a 7-day washout period (without antihypertensives), they had a baseline standard PET and dialysis adequacy assessment performed. Subsequently, they were randomly allocated to receive the first of three study drugs (losartan, prazosin, and verapamil), which were administered orally for a 7-day period. Immediately after each drug period, patients had a new 3-day washout and subsequently started the next drug, until they had received each of the three drugs. On the last day of administration of each drug, patients were subjected to a new PET and adequacy of dialysis evaluation.


RESULTS
None of the studied drugs significantly modified the peritoneal transport of creatinine, glucose, urea, sodium, potassium, or total protein as evaluated by PET. Verapamil significantly increased peritoneal CrCl [51.3 (44.3 - 53.3) vs baseline 45.8 (41.4 - 50.5) L/week/ 1.73 m2, p < 0.05], weekly Kt/V urea [1.75 (1.60 - 1.78) vs baseline 1.59 (1.54 - 1.73), p < 0.05], and drained dialysate volume [8.80 (8.30 - 8.96) vs baseline 8.44 (8.20 - 8.50) L/day, p < 0.05].


CONCLUSIONS
Oral administration of losartan, prazosin, and verapamil did not modify the peritoneal transport of solutes during a 4-hour PET. Oral verapamil significantly increased CrCl, Kt/V urea, and 24-hour drained dialysate volume. It is most likely that verapamil increases peritoneal (hydraulic) conductivity, and then net ultrafiltration volume and convective transport of urea, creatinine, and protein. Verapamil could be considered as an alternative in patients requiring increased dialysis dose and/or ultrafiltration.
Rojas-Campos
Enrique
E
Unidad de Investigación Medica en Epidemiología Clínica, Hospital de Especialidades, CMNO, IMSS, Guadalajara, Jalisco, Mexico.
Cortés-Sanabria
Laura
L
Martínez-Ramírez
Héctor R
HR
González
Liliana
L
Martín-del-Campo
Fabiola
F
González-Ortiz
Manuel
M
Cueto-Manzano
Alfonso M
AM
D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001692:Biological Transport / Q000187:drug effects; D003401:Creatine / Q000378:metabolism; D018592:Cross-Over Studies; D015314:Dialysis Solutions / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011224:Prazosin / Q000008:administration & dosage*; D012964:Sodium / Q000378:metabolism; D016896:Treatment Outcome; D014508:Urea / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage; D014700:Verapamil / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D015314:Dialysis Solutions; D014665:Vasodilator Agents; D014508:Urea; D012964:Sodium; D014700:Verapamil; D005947:Glucose; D019808:Losartan; D003401:Creatine; D011188:Potassium; D011224:Prazosin