Pharmacokinetics of calcitriol and maxacalcitol administered into peritoneal dialysate bags in peritoneal dialysis patients.
OBJECTIVE
It is well known that injection of calcitriol (CT) or maxacalcitol (OCT) is very effective in hemodialysis patients with secondary hyperparathyroidism (2HPT). However, it is difficult to use these drugs with peritoneal dialysis (PD) patients with 2HPT because these drugs must be injected two or three times per week. The objective of the present study was to evaluate the stability of physiological activities of CT and OCT in PD bags and to determine the CT or OCT dosage for intraperitoneal (IP) administration.


METHODS
We added CT 1.5 microg or OCT 10 microg to Dianeal PD-2 (approximate pH = 5.0, calcium = 0.87 mmol/L; Baxter,Tokyo, Japan), Midpeliq 250 (approximate pH = 7.0, Ca = 1.0 mmol/L;Terumo Corporation, Tokyo, Japan), and Peritoliq 250 (approximate pH = 5.5, Ca = 1.0 mmol/L; Terumo Corp.). Dialysis solutions were collected from the PD bags at 0, 1, 4, 8, 12, 24, 48, and 72 hours after addition of CT and OCT. The activities of CT and OCT in the dialysis effluent were measured by radioimmunoassay. The levels of serum and effluent OCT after a single IP administration of 10 microg OCT were examined in 4 PO patients with advanced 2HPT.


RESULTS
Although the levels of CT and OCT in PD bags made of polyvinyl resins decreased by 70% - 75% immediately after injection, levels in PD bags made of polypropylene resins decreased only slightly. The concentration of CT mixed into the acidic solution in glass containers was stable; the decreased concentration of CT in the PD solution might be due to adsorption onto polyvinyl resins. The maximum serum concentration after IP administration of 10 microg OCT was 750 pg/mL after 5 minutes, and remained at 500 pg/mL at 60 minutes. These results show good peritoneal transport of OCT but not rapid disappearance, unlike intravenous administration.


CONCLUSIONS
If peritoneal administration of vitamin D derivatives is contemplated, it is important to select the composition of PD bag resins, type of vitamin D analog, and time lag to use when deciding the dosage of injectable vitamin D preparations, such as OCT or CT, for IP administration to PD patients. It appears that IP administration in overnight dwells might be useful for PD patients as a complementary vitamin D preparation.
Hamada
Chieko
C
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Hayashi
Kayo
K
Shou
Ichiyu
I
Inaba
Masanori
M
Ro
Yuuki
Y
Io
Hiroaki
H
Maeda
Kunimi
K
Fukui
Mitsumine
M
Tomino
Yasuhiko
Y
D001202:Ascitic Fluid / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D015314:Dialysis Solutions / Q000494:pharmacology*; D004339:Drug Compounding / Q000295:instrumentation; D004349:Drug Packaging; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy; D010530:Peritoneal Dialysis / Q000295:instrumentation*; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D015314:Dialysis Solutions; D002117:Calcitriol; C051883:maxacalcitol