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Pharmacokinetics of Olmesartan Medoxomil in Pediatric Patients with Hypertension

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Abstract

Background: The prevalence and importance of hypertension in younger patients is becoming increasingly recognized; however, only a limited number of clinical trials have been conducted in the pediatric population.

Objective: The aim of this study was to characterize the pharmacokinetics and short-term safety of olmesartan medoxomil in children and adolescents with hypertension.

Methods: An open-label, multicenter, single-dose study was conducted in children and adolescents aged 12 months–16 years who were receiving treatment for hypertension or, if not currently treated for hypertension, had either a systolic blood pressure (SBP) or diastolic blood pressure (DBP) ≤95th percentile, or SBP or DBP ≤90th percentile if diabetic or with a family history of hypertension. Patients were stratified by age: 12–23 months (Group 1; none enrolled), 2–5 years (Group 2; n = 4), 6–12 years (Group 3; n = 10), and 13–16 years (Group 4; n = 10). All patients received a single oral dose of olmesartan medoxomil based on the individual’s age and bodyweight. Patients aged <6 years received an oral suspension of olmesartan medoxomil at a dose of 0.3 mg/kg of bodyweight (not to exceed 20 mg), those aged ≤6 years who weighed ≤35 kg received olmesartan medoxomil 40 mg tablets, and those who weighed <35 kg received olmesartan medoxomil 20 mg tablets.

Results: In Groups 2, 3, and 4, the weight-adjusted apparent total body clearance (CL/F) of olmesartan medoxomil was 0.100 ± 0.034, 0.062 ± 0.020, and 0.072± 0.022L/h/kg, respectively, and the weight-adjusted apparent volume of distribution (Vd/F) was 0.32± 0.16, 0.33 ±0.14, and 0.49±0.23 L/kg, respectively. CL/F and Vd/F in Groups 3 and 4 were not significantly different. Statistical comparisons between Groups 3 or 4 and Group 2 were not performed due to the small sample size of Group 2 (n =4). Plasma elimination half-life and time to maximum plasma concentration were similar across the three groups. In Groups 3 and 4, considerable interindividual variability was seen in maximum plasma concentration (Cmax), area under the curve (AUC) from time zero to the last measurable concentration, and apparent clearance, with AUC and Cmax approximately 30% greater in Group 3. Four of 24 (16.7%) patients experienced treatment-emergent adverse events that were all mild in severity and considered not drug-related. No deaths, serious adverse events, or discontinuations due to adverse events occurred in the study.

Conclusions: Olmesartan medoxomil was well tolerated and demonstrated a pharmacokinetic profile in pediatric patients similar to that of adults when adjusted for body size.

Trial Registration: ClinicalTrials.gov identifier: NCT00151814

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Acknowledgments

We acknowledge a grant from the Pediatric Pharmacology Research Unit Network for partially supporting the work performed at the Arkansas Children’s Hospital, Little Rock, AR, USA; University of Louisville, Louisville, KY, USA; Rainbow Babies and Children’s Hospital, Cleveland, OH, USA; Children’s Mercy Hospital, Kansas City, MO, USA; and the University of Utah, Salt Lake City, UT, USA.

Daiichi Sankyo, Inc. provided support for this study. We would like to thank Radha Basavapathruni, MSPH, formerly employed by Daiichi Sankyo, Inc., for involvement in study management, and Alan J. Klopp, PhD, and Blair Jarvis, MSc, of inScience Communications, Springer Healthcare, for providing medical writing support funded by Daiichi Sankyo, Inc.

Thomas G. Wells, MD, served as an investigator for the study discussed in the article and received medical writing support, which were both supported by Daiichi Sankyo, Inc. Janice E. Sullivan, MD, received pharmaceutical support from Daiichi Sankyo, Inc. to conduct the study. Jeffrey Blumer, MD, received a grant from the National Institutes of Health (NIH), Pediatric Pharmacology Research Unit grant 3U10HDA31323-13;B.NA, which is unrelated to the study discussed in this article. Joseph R. Sherbotie, MD, received pharmaceutical support from Daiichi Sankyo, Inc. to conduct the study but no direct financial support was provided to the contributors. Shashank Rohatagi, PhD, and Reinilde Heyrman, MD, were employed by Daiichi Sankyo, Inc., the sponsor of the study, at the time the study was conducted. SaeHeum Song, PhD, and Daniel E. Salazar, PhD, FCP, are employees of Daiichi Sankyo, Inc., the sponsor of the study. SaeHeum Song holds stock appreciation rights/restricted stock units and Daniel Salazar holds stock options for Daiichi Sankyo, Inc. Douglas L. Blowey, MD, has no conflicts of interest to disclose.

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Authors and Affiliations

  1. Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, 1 Children’s Way, Little Rock, Arkansas, AR 72202, USA

    Thomas G. Wells

  2. The Children’s Mercy Hospital, University of Missouri-Kansas City, Kansas City, Missouri, USA

    Douglas L. Blowey

  3. Kosair Children’s Hospital, University of Louisville, Louisville, Kentucky, USA

    Janice E. Sullivan

  4. College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio, USA

    Jeffrey Blumer

  5. University of Utah School of Medicine, Salt Lake City, Utah, USA

    Joseph R. Sherbotie

  6. Daiichi Sankyo, Inc., Parsippany, New Jersey, USA

    SaeHeum Song, Shashank Rohatagi, Reinilde Heyrman & Daniel E. Salazar

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  1. Thomas G. Wells
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Correspondence to Thomas G. Wells.

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Wells, T.G., Blowey, D.L., Sullivan, J.E. et al. Pharmacokinetics of Olmesartan Medoxomil in Pediatric Patients with Hypertension. Pediatr Drugs 14, 401–409 (2012). https://doi.org/10.1007/BF03262420

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