title: Use of ketoconazole to probe the pathogenetic importance of 1,25-dihydroxyvitamin D in absorptive hypercalciuria.
abstract: Ketoconazole was used to probe the pathogenetic importance of the serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentration in 19 patients with well characterized absorptive hypercalciuria (AH). Patients were studied while receiving a constant metabolic diet before and after 2 weeks of ketoconazole administration (600 mg daily). Twelve of the patients were classified as ketoconazole responders, because in conjunction with a reduction of serum 1,25-(OH)2D from 113 +/- 36 to 70 +/- 26 pmol/L, intestinal 47Ca absorption decreased from 76.3 +/- 8.1% to 61.9 +/- 7.7%, and 24-h urinary Ca excretion declined from 7.6 +/- 1.4 to 5.7 +/- 1.1 mmol (P < 0.001 each). In these patients, intestinal 47Ca absorption was directly correlated with serum 1,25-(OH)2D levels and 24-h Ca excretion. In another group of 7 patients, termed ketoconazole nonresponders, despite reduction of 1,25-(OH)2D from 122 +/- 36 to 84 +/- 17 pmol/L (P = 0.015), there was no significant change in intestinal Ca absorption (76.0 +/- 8.2% to 72.1 +/- 10.6%) or 24-h urinary Ca excretion (7.3 +/- 1.3 to 7.2 +/- 1.0 mmol). In these patients, neither intestinal Ca absorption nor urinary Ca excretion was correlated with serum 1,25-(OH)2D levels. It, thus, appears that AH is a heterogeneous disorder comprised of both vitamin D-dependent and vitamin D-independent subsets. Although useful to probe the pathogenesis of AH, chronic treatment with ketoconazole is not recommended because of its generalized effects in inhibiting steroid synthesis.
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
authors: N A
authors: NA
authors: Breslau
authors: G M
authors: GM
authors: Preminger
authors: B V
authors: BV
authors: Adams
authors: J
authors: J
authors: Otey
authors: C Y
authors: CY
authors: Pak
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine*; D002784:Cholesterol / Q000097:blood; D004100:Dihydroxycholecalciferols / Q000502:physiology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007408:Intestinal Absorption; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D014280:Triglycerides / Q000097:blood
chemical_list: D004100:Dihydroxycholecalciferols; D012739:Gonadal Steroid Hormones; D014280:Triglycerides; D002784:Cholesterol; D007654:Ketoconazole; D002118:Calcium