Trial reportClinical pharmacokinetics2007
Pharmacokinetics of cinacalcet hydrochloride when administered with ketoconazole.
Trial report in Clinical pharmacokinetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Evocalcet in patients with primary hyperparathyroidism: an open-label, single-arm, multicenter, 52-week, dose-titration phase III study.Journal of bone and mineral metabolism · 2020Trial
- Trial
- Pharmacokinetics, Pharmacodynamics, and Safety of Evocalcet (KHK7580), a Novel Calcimimetic Agent: An Open-Label, Single- and Multiple-Dose, Phase I Trial in Healthy Chinese Subjects.Drug design, development and therapy · 2024Article
- Physiologically-Based Pharmacokinetic Models of CYP2D6 Substrate and Inhibitors Nebivolol, Cinacalcet and Mirabegron to Simulate Drug-Drug Interactions.European journal of drug metabolism and pharmacokinetics · 2022Article
- Pharmacogenetic and safety analysis of cinacalcet hydrochloride in healthy Chinese subjects.Annals of translational medicine · 2020Article
- Evocalcet prevents ectopic calcification and parathyroid hyperplasia in rats with secondary hyperparathyroidism.PloS one · 2020Article
- The Cancer Drug Fraction of Metabolism Database.CPT: pharmacometrics & systems pharmacology · 2019Article
- Comment on: Pharmacokinetics, Pharmacodynamics, and Safety of the Novel Calcimimetic Agent Evocalcet in Healthy Japanese Subjects: First-in-Human Phase I Study.Clinical drug investigation · 2019Article
- Assessment of CYP-Mediated Drug Interactions for Evocalcet, a New Calcimimetic Agent, Based on In Vitro Investigations and a Cocktail Study in Humans.Clinical and translational science · 2019Article
- Article
- A Model for Predicting the Interindividual Variability of Drug-Drug Interactions.The AAPS journal · 2017Article
- Coprescription of tamoxifen and medications that inhibit CYP2D6.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010Review
- Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride.Clinical pharmacokinetics · 2009Review
- Cinacalcet in HIV haemodialysis patients.NDT plus · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveThe calcimimetic cinacalcet hydrochloride (cinacalcet) is used for treatment of patients with chronic kidney disease with secondary hyperparathyroidism, a population that commonly receives multiple concurrent medications. Cinacalcet is eliminated primarily via oxidative metabolism mediated, in part, through cytochrome P450 (CYP) 3A4. Thus, the potential for an inhibitor of CYP3A4 to alter the pharmacokinetics of cinacalcet is of clinical importance. The objective of this study was to evaluate the pharmacokinetics of cinacalcet during treatment with a potent CYP3A4 inhibitor, ketoconazole. SUBJECTS AND
methodsTwenty-four healthy subjects were enrolled in an open-label, crossover, phase I study to receive a single oral dose of cinacalcet (90 mg) alone and with 7 days of ketoconazole (200mg twice daily). Blood samples for pharmacokinetics were collected for up to 72 hours postdose. Cinacalcet plasma concentration-time data were analysed by noncompartmental methods. Pharmacokinetic parameters were analysed using a crossover ANOVA model that included subjects who completed both treatment arms.
resultsTwenty subjects completed both treatment arms. The mean area under the plasma concentration-time curve of cinacalcet increased 2.3-fold (90% CI 1.92, 2.67) [range 1.15- to 7.12-fold] and the mean maximum plasma concentration increased 2.2-fold (90% CI 1.67, 2.78) [range 0.904- to 10.8-fold] when administered with ketoconazole, relative to when administered alone. The time to reach the maximum plasma concentration was not significantly affected, and the terminal elimination half-lives were similar between treatments.
conclusionsCo-administration of a potent CYP3A4 inhibitor moderately increased cinacalcet exposure in study subjects. This suggests that clinicians should monitor parathyroid hormone and calcium concentrations when a patient receiving cinacalcet initiates or discontinues therapy with a strong CYP3A4 inhibitor.
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