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Effects of i.v. and oral 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in dogs with chronic renal failure.
Nephrol Dial Transplant. 2002; 17 Suppl 10:46-52.ND

Abstract

BACKGROUND

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) has been used for the treatment of secondary hyperparathyroidism (2HPT) associated with chronic renal failure (CRF). However, hypercalcaemia frequently precludes the administration of ideal doses of 1,25(OH)(2)D(3). 1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is an analogue of 1,25(OH)(2)D(3) with less calcaemic activity. Several investigators have reported the effect of this analogue on suppressing parathyroid hormone (PTH) in vitro and in vivo in rats and dogs.

METHODS AND RESULTS

The first experiments were designed to compare the relative potency of an i.v. injection of OCT and 1,25(OH)(2)D(3) (i.v. OCT vs i.v. 1,25(OH)(2)D(3)) on serum PTH and ionized calcium (ICa). A single dose of OCT (5 microg/kg) to uraemic dogs suppressed PTH by 81% without a statistical significant change in serum ICa. On the other hand, any of the effective doses of 1,25(OH)(2)D(3) on PTH suppression were hypercalcaemic. The intermittent administration of OCT (0.1 microg/kg) or 1,25(OH)(2)D(3) (0.025 microg/kg), three times per week i.v. suppressed serum PTH by 89 or 77%, respectively without hypercalcaemia. To evaluate OCT as an oral drug, it was given intermittently (three times per week) to a group of six dogs for a period of 4 weeks. Subsequently, it was changed to a daily administration (0.05 microg/kg) for a period of 2 weeks. Finally the dose was reduced to 0.025 microg/kg. Daily OCT 0.05 microg/kg suppressed serum PTH by 67%. Subsequently, 0.025 microg/kg maintained serum PTH within the normal range without hypercalcaemia for 4 weeks. The time course of serum OCT concentrations following a single i.v. or oral OCT dose to uraemic dogs showed that oral OCT was rapidly absorbed and reached maximum plasma concentration and its disappearance from blood was similar to that of i.v. injection.

CONCLUSIONS

In conclusion, our results suggest that OCT is a useful vitamin D(3) analogue, with a potentially larger therapeutic window than that of i.v. 1,25(OH)(2)D(3) and which is available for i.v./oral, in the management of 2HPT.

Authors+Show Affiliations

Chugai Pharmaceutical Co Ltd, Gotemba, Shizuoka, Japan. takahashifma@chugai-pharm.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

12386269

Citation

Takahashi, Fumiaki, et al. "Effects of I.v. and Oral 1,25-dihydroxy-22-oxavitamin D(3) On Secondary Hyperparathyroidism in Dogs With Chronic Renal Failure." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 17 Suppl 10, 2002, pp. 46-52.
Takahashi F, Furuichi T, Yorozu K, et al. Effects of i.v. and oral 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in dogs with chronic renal failure. Nephrol Dial Transplant. 2002;17 Suppl 10:46-52.
Takahashi, F., Furuichi, T., Yorozu, K., Kawata, S., Kitamura, H., Kubodera, N., & Slatopolsky, E. (2002). Effects of i.v. and oral 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in dogs with chronic renal failure. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 17 Suppl 10, 46-52.
Takahashi F, et al. Effects of I.v. and Oral 1,25-dihydroxy-22-oxavitamin D(3) On Secondary Hyperparathyroidism in Dogs With Chronic Renal Failure. Nephrol Dial Transplant. 2002;17 Suppl 10:46-52. PubMed PMID: 12386269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of i.v. and oral 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in dogs with chronic renal failure. AU - Takahashi,Fumiaki, AU - Furuichi,Tatsuya, AU - Yorozu,Keigo, AU - Kawata,Setsu, AU - Kitamura,Hidetomo, AU - Kubodera,Noboru, AU - Slatopolsky,Eduardo, PY - 2002/10/19/pubmed PY - 2003/4/18/medline PY - 2002/10/19/entrez SP - 46 EP - 52 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol. Dial. Transplant. VL - 17 Suppl 10 N2 - BACKGROUND: 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) has been used for the treatment of secondary hyperparathyroidism (2HPT) associated with chronic renal failure (CRF). However, hypercalcaemia frequently precludes the administration of ideal doses of 1,25(OH)(2)D(3). 1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is an analogue of 1,25(OH)(2)D(3) with less calcaemic activity. Several investigators have reported the effect of this analogue on suppressing parathyroid hormone (PTH) in vitro and in vivo in rats and dogs. METHODS AND RESULTS: The first experiments were designed to compare the relative potency of an i.v. injection of OCT and 1,25(OH)(2)D(3) (i.v. OCT vs i.v. 1,25(OH)(2)D(3)) on serum PTH and ionized calcium (ICa). A single dose of OCT (5 microg/kg) to uraemic dogs suppressed PTH by 81% without a statistical significant change in serum ICa. On the other hand, any of the effective doses of 1,25(OH)(2)D(3) on PTH suppression were hypercalcaemic. The intermittent administration of OCT (0.1 microg/kg) or 1,25(OH)(2)D(3) (0.025 microg/kg), three times per week i.v. suppressed serum PTH by 89 or 77%, respectively without hypercalcaemia. To evaluate OCT as an oral drug, it was given intermittently (three times per week) to a group of six dogs for a period of 4 weeks. Subsequently, it was changed to a daily administration (0.05 microg/kg) for a period of 2 weeks. Finally the dose was reduced to 0.025 microg/kg. Daily OCT 0.05 microg/kg suppressed serum PTH by 67%. Subsequently, 0.025 microg/kg maintained serum PTH within the normal range without hypercalcaemia for 4 weeks. The time course of serum OCT concentrations following a single i.v. or oral OCT dose to uraemic dogs showed that oral OCT was rapidly absorbed and reached maximum plasma concentration and its disappearance from blood was similar to that of i.v. injection. CONCLUSIONS: In conclusion, our results suggest that OCT is a useful vitamin D(3) analogue, with a potentially larger therapeutic window than that of i.v. 1,25(OH)(2)D(3) and which is available for i.v./oral, in the management of 2HPT. SN - 0931-0509 UR - https://www.unboundmedicine.com/medline/citation/12386269/Effects_of_i_v__and_oral_125_dihydroxy_22_oxavitamin_D_3__on_secondary_hyperparathyroidism_in_dogs_with_chronic_renal_failure_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/17.suppl_10.46 DB - PRIME DP - Unbound Medicine ER -