The minimal impact of food on the pharmacokinetics of ridaforolimus

Stroh, Mark; Li, Xiaodong; Marsilio, Sabrina; Panebianco, Deborah; Johnson‐Levonas, Amy O.; Juan, Axel; Orford, Keith; Agrawal, Nancy G. B.; Trucksis, Michele; Wagner, John A.; Murphy, Gail; Iwamoto, Marian

doi:10.1007/s00280-012-1897-8

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…At therapeutic dose levels, plasma ridaforolimus levels are commonly at or near the limit of assay detection (lower limit of quantitation, LLOQ) for the plasma assay was 0.1 ng/mL); accordingly, whole blood pharmacokinetic (PK) parameters are provided for ridaforolimus. Since the proportion of ridaforolimus in plasma relative to whole blood is influenced by the saturable binding event, there are correspondingly less than proportional increases in whole blood exposure with dose, especially above the investigated Phase III 40 mg oral dose level (NCT00538239) . The apparent whole blood terminal elimination half‐life (t 1/2 ) is approximately 56 hours, and steady‐state trough levels are generally approached after administration of 5 consecutive daily doses (q.d.…”

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confidence: 99%

Lack of meaningful effect of ridaforolimus on the pharmacokinetics of midazolam in cancer patients: Model prediction and clinical confirmation

Stroh

Talaty

Sandhu

et al. 2014

The Journal of Clinical Pharma

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Ridaforolimus, a unique non-prodrug analog of rapamycin, is a potent inhibitor of mTOR under development for cancer treatment. In vitro data suggest ridaforolimus is a reversible and time-dependent inhibitor of CYP3A. A model-based evaluation suggested an increase in midazolam area under the curve (AUC(0- ∞)) of between 1.13- and 1.25-fold in the presence of therapeutic concentrations of ridaforolimus. The pharmacokinetic interaction between multiple oral doses of ridaforolimus and a single oral dose of midazolam was evaluated in an open-label, fixed-sequence study, in which cancer patients received a single oral dose of 2 mg midazolam followed by 5 consecutive daily single oral doses of 40 mg ridaforolimus with a single dose of 2 mg midazolam with the fifth ridaforolimus dose. Changes in midazolam exposure were minimal [geometric mean ratios and 90% confidence intervals: 1.23 (1.07, 1.40) for AUC(0-∞) and 0.92 (0.82, 1.03) for maximum concentrations (C(max)), respectively]. Consistent with model predictions, ridaforolimus had no clinically important effect on midazolam pharmacokinetics and is not anticipated to be a perpetrator of drug-drug interactions (DDIs) when coadministered with CYP3A substrates. Model-based approaches can provide reasonable estimates of DDI liability, potentially obviating the need to conduct dedicated DDI studies especially in challenging populations like cancer patients.

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confidence: 99%

Lack of meaningful effect of ridaforolimus on the pharmacokinetics of midazolam in cancer patients: Model prediction and clinical confirmation

Stroh

Talaty

Sandhu

et al. 2014

The Journal of Clinical Pharma

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“…The drugs used in DES target cell growth and neo-intimal proliferation to prevent in-stent restenosis and are also used for certain oncology and immunosuppression indications. 11 , 12 The effect of these potent long-acting drugs on the breastfeeding infant was a concern. The effects of antiproliferative drugs used in these stents have, to the best of our knowledge, not been studied in lactating mothers.…”

Section: Discussionmentioning

confidence: 99%

Clinical considerations during spontaneous coronary artery dissection in the post-partum period: a case report

Schamroth Pravda,

Houri,

Kornowski

et al. 2023

European Heart Journal - Case Reports

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Background Spontaneous coronary artery dissection (SCAD) is a common and under-recognized cause of myocardial infarction during the post-partum period. Case Summary We report a case of a young women presenting with chest pain in the post-partum period. Her clinical appearance was that of a myocardial infarction and angiography was indicative of a Type 2 spontaneous coronary artery dissection (SCAD). The patients had persistent chest pain, reduced left ventricular function and critical left anterior descending artery stenosis. Percutaneous coronary intervention was done with caution. Shared decision making with the patient helped guide the medical treatment plan and follow up. Discussion We discuss the clinical considerations surrounding the management of this patient.

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“…Previous studies have consistently confirmed the safety and tolerability of ridaforolimus in patients. Notably, a single 40 mg dose of ridaforolimus was well tolerated in healthy adult males (Stroh et al, 2012a), and it exhibited consistent absorption rates regardless of whether it was administered with a light or high-fat breakfast. Furthermore, ridaforolimus did not prolong the corrected QT interval (QTc) in patients with advanced cancer (Lush et al, 2012).…”

Section: Introductionmentioning

confidence: 98%

Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review

Wang,

Qiu,

Yang

et al. 2024

Front. Pharmacol.

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Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus’s clinical applications.

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The minimal impact of food on the pharmacokinetics of ridaforolimus

Cited by 6 publications

References 13 publications

Lack of meaningful effect of ridaforolimus on the pharmacokinetics of midazolam in cancer patients: Model prediction and clinical confirmation

Lack of meaningful effect of ridaforolimus on the pharmacokinetics of midazolam in cancer patients: Model prediction and clinical confirmation

Clinical considerations during spontaneous coronary artery dissection in the post-partum period: a case report

Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review

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