Modification of the pharmacokinetics of cyclosporine a and metabolites by the concomitant use of neoral and diltiazem or ketoconazol in stable adult kidney transplants

Foradori, A; Mezzano, Sergio; Videla, C; Pefaur, Jacqueline; Elberg, A

doi:10.1016/s0041-1345(98)00393-5

Cited by 39 publications

(14 citation statements)

References 10 publications

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“…However, at high CsA concentrations, an alternative metabolic pathway was detectable, not inhibited by diltiazem (Preuner et al, 1998). Other studies also suggested that diltiazem enhances the absorption of CsA (Foradori et al, 1998). The phenomenon was similarly observed with verapamil (Tortorice et al, 1990).…”

Section: Discussionmentioning

confidence: 80%

Population Pharmacokinetics of Cyclosporine in Clinical Renal Transplant Patients

Cui²,

Guo³

et al. 2005

Drug Metab Dispos

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Section: Discussionmentioning

confidence: 80%

Population Pharmacokinetics of Cyclosporine in Clinical Renal Transplant Patients

Cui²,

Guo³

et al. 2005

Drug Metab Dispos

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“…20,94 Indeed, CYP3A4 showed a marked increase in the oral bioavailability of cyclosporine. 95 The absorption of large peptides, cholecystokinin/enkephalin analogs and protein drugs was improved by using protease inhibitor cocktails with attention to specific absorption sites. 96–98 …”

Section: Approaches For Optimizing Uptake and Bioavailabilitymentioning

confidence: 99%

Past, Present, and Future Technologies for Oral Delivery of Therapeutic Proteins

Singh

Lillard

2008

Journal of Pharmaceutical Sciences

165

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Biological drugs are usually complex proteins and cannot be orally delivered due to problems related to degradation in the acidic and protease-rich environment of the gastrointestinal (GI) tract. The high molecular weight of these drugs often results in poor absorption into the periphery when administered orally. The most common route of administration for these therapeutic proteins is injection. Most of these proteins have short serum half-lives and need to be administered frequently or in high doses to be effective. So, difficulties in the administration of protein-based drugs provides the motivation for developing drug delivery systems (DDSs) capable of maintaining therapeutic drug levels without side effects as well as traversing the deleterious mucosal environment. Employing a polymer as an entrapment matrix is a common feature among the different types of systems currently being pursued for protein delivery. Protein release from these matrices can occur through various mechanisms, such as diffusion through or erosion of the polymer matrix, and sometimes a combination of both. Encapsulation of proteins in liposomes has also been a widely investigated technology for protein delivery. All of these systems have merit and our worthy of pursuit.

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“…Diltiazem and verapamil are classified as "moderate" CYP3A inhibitors, and evidence points to the dihydropyridines as inhibitors of CYP3A as well (9). In fact, diltiazem is occasionally used with transplant patients to allow the use of smaller (i.e., less expensive) doses of cyclosporine (7,10). Siller-Matula et al (8) measured VASP levels in 200 consecutive patients undergoing stent implantation and found that the PRI was significantly higher (implying less clopidogrel effect on platelets) among patients who were receiving calcium-channel antagonists compared with patients who were not.…”

Section: See Page 1557mentioning

confidence: 99%

Clopidogrel and Calcium-Channel Antagonists

Kleiman

2008

Journal of the American College of Cardiology

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The medical management of patients with coronary artery disease is currently dominated by strategies to alter lipid levels and to inhibit platelet aggregation and activation. In fact, one can make a very strong argument that coronary artery stenting would never have achieved its current level of popularity and success had it not been for the pioneering work done by Colombo et al. (1) using the thienopyridine ticlopidine. Ticlopidine has been almost universally replaced by clopidogrel, a second-generation thienopyridine that is considerably better tolerated. Despite clopidogrel's success for patients receiving intracoronary stents and for patients with acute coronary syndromes, its use is hampered by the consistent finding that as many as 1 of 4 patients receiving clopidogrel have little evidence of antiplatelet response to the drug (2-4). The phenotype of clopidogrel "resistance" has been associated with an increased risk of cardiovascular events (3,5) and of stent thrombosis; several prospective investigations are being performed to verify these findings. See page 1557Clopidogrel is a pro-drug and is converted in the liver by the members of the cytochrome P450 (CYP) family (predominantly the 3A and 2C groups) to a series of metabolites, the last of which, the thiol metabolite, is an antagonist of the platelet purinergic receptor known as P2Y12 (6). As reviewed elsewhere, ligation of P2Y12 by the active metabolite of clopidogrel prevents adenoside diphosphate (ADP) from activating the receptor and prevents a chain of events that would otherwise lead to platelet shape change, secretion, and aggregation. Among the many tests that have been proposed to assess clopidogrel's biologic activity, a recent addition has been the development of assays for vasodilator stimulated phosphoprotein (VASP). The VASP assay developed by Schwarz et al. (7) appears to capture most of the activity of P2Y12 and has the advantage that, unlike functional assays such as platelet aggregation, it is pathwayspecific for P2Y12 activation. When ADP ligates P2Y12, G i protein signaling pathways reduce intracellular levels of cyclic adenosine monophosphate (cAMP), which in turn leads to decreased phosphorylation of VASP. Because phosphorylation inactivates VASP, high levels of dephosphorylated VASP reflect high levels of P2Y12 occupancy by ADP whereas high levels of phosphorylated VASP reflect blockade of P2Y12. The relationship is generally regarded as being linear. For clinical purposes, levels of VASP phosphorylation are indexed for maximal VASP phosphorylation (stimulated by prostaglandin E1) and are reported as the platelet reactivity index (PRI), or VASP phosphorylation index.In this issue of the Journal, Siller-Matula et al. (8) assessed whether calcium-channel antagonists, specifically verapamil and a number of dihydropyridines, altered the effect of clopidogrel on platelets in patients undergoing coronary arterial stenting. The interaction between calciumchannel antagonists and the metabolism of other drugs is well documented. Diltiazem ...

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Modification of the pharmacokinetics of cyclosporine a and metabolites by the concomitant use of neoral and diltiazem or ketoconazol in stable adult kidney transplants

Cited by 39 publications

References 10 publications

Population Pharmacokinetics of Cyclosporine in Clinical Renal Transplant Patients

Population Pharmacokinetics of Cyclosporine in Clinical Renal Transplant Patients

Past, Present, and Future Technologies for Oral Delivery of Therapeutic Proteins

Clopidogrel and Calcium-Channel Antagonists

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