The relative bioavailability of 2 prototype fixed‐dose combination formulations for amlodipine and rosuvastatin in healthy white and Chinese subjects

Nwe, Htar H.; Bullman, Jonathan; Joshi, Shashidhar; Stylianou, Annie; Kapsi, Shiva G.

doi:10.1002/cpdd.214

Cited by 3 publications

(2 citation statements)

References 15 publications

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“…During period 2 of both parts of this study, upadacitinib 30 mg was dosed alone once daily for 10 days and rosuvastatin (in part 1) or atorvastatin (in part 2) was administered 1 hour following upadacitinib dosing on day 7. Part 1 was conducted in 12 healthy subjects, and part 2 was conducted in 24 healthy subjects, given the higher within‐subject variability in atorvastatin pharmacokinetics compared to rosuvastatin 29,30 . All study drugs were administered orally with ≈240 mL of water under nonfasting conditions.…”

Section: Methodsmentioning

confidence: 99%

“…Part 1 was conducted in 12 healthy subjects, and part 2 was conducted in 24 healthy subjects, given the higher within‐subject variability in atorvastatin pharmacokinetics compared to rosuvastatin. 29 , 30 All study drugs were administered orally with ≈240 mL of water under nonfasting conditions. Rosuvastatin and atorvastatin were administered in period 2 one hour after administration of upadacitinib extended‐release formulation to account for the delay in upadacitinib absorption from the extended‐release formulation under nonfasting conditions.…”

Section: Methodsmentioning

confidence: 99%

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Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects

Mohamed

Coppola

Tian

et al. 2021

Clinical Pharm in Drug Dev

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This phase 1, 2-part, 2-period, open-label, drug-drug interaction study evaluated the potential for pharmacokinetic interactions between upadacitinib and rosuvastatin, an organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein substrate, or atorvastatin, a cytochrome P450 3A, OATP1B1, and OATP1B3 substrate, in 36 healthy volunteers. During period 1, a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered on day 1, followed by a washout period of 5 days. During period 2, once-daily doses of upadacitinib extended-release (30 mg) were administered on days 1 to 10, and a single dose of rosuvastatin (5 mg; part 1) or atorvastatin (10 mg; part 2) was administered 1 hour after the upadacitinib dose on day 7. Serial blood samples were collected for assays of drug concentrations. In Part 1, rosuvastatin maximum observed plasma concentration (C max ) and area under the plasma concentration-time curve from time 0 to infinity (AUC inf ) were 23% and 33% lower, respectively, when administered with upadacitinib relative to when administered alone. In part 2, atorvastatin C max and AUC inf was 11% and 23% lower, respectively, when administered with upadacitinib relative to when administered alone. The C max and AUC inf of the active metabolite ortho-hydroxyatorvastatin remained unchanged. Administration of a single 5-mg dose of rosuvastatin or a single 10-mg dose of atorvastatin had no relevant effect on upadacitinib C max or area under the plasma concentrationtime curve. These results demonstrated that upadacitinib has no clinically relevant effect on the pharmacokinetics of rosuvastatin and atorvastatin or on substrates transported by OATP1B or breast cancer resistance protein.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects

Mohamed

Coppola

Tian

et al. 2021

Clinical Pharm in Drug Dev

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Key Pharmacokinetic Essentials of Fixed-Dosed Combination Products: Case Studies and Perspectives

2017

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Fixed-dose combinations are gaining popularity because they provide convenience while enhancing patient compliance. Literature examples suggest that many fixed-dose combinations are being rationalized and investigated for their potential utility in therapy. This article provides an introspection into the pharmacokinetic essentials that need to be considered prior to implementing a fixed-dose combination strategy. While the drug-drug interaction potential is an important question for the two drugs in a fixed-dose combination, the occurrence of a drug-drug interaction in itself is not a negative outcome for the proposed fixed-dose combination. However, the magnitude of a drug-drug interaction may require a re-assessment of the doses of the two drugs in a fixed-dose combination. Several case studies are provided and discussed to provide a broad perspective on the topic along with a representative framework and strategy on the development of fixed-dose combinations using key pharmacokinetic parameters.

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Comparative efficacy of fixed-dose statin and antihypertensive agent combinations: A network meta-analysis of randomized controlled trials

Bellos

Pergialiotis

Perrea

2021

Vascular Pharmacology

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The relative bioavailability of 2 prototype fixed‐dose combination formulations for amlodipine and rosuvastatin in healthy white and Chinese subjects

Cited by 3 publications

References 15 publications

Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects

Effect of Upadacitinib on the Pharmacokinetics of Rosuvastatin or Atorvastatin in Healthy Subjects

Key Pharmacokinetic Essentials of Fixed-Dosed Combination Products: Case Studies and Perspectives

Comparative efficacy of fixed-dose statin and antihypertensive agent combinations: A network meta-analysis of randomized controlled trials

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