Pharmacokinetic of Everolimus and Atorvastatin Co-administration

Study Overview
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Brief Summary
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Hypothesis : In renal transplantation recipient who received immunosuppressive drug certican and have hypercholesterolemia will get lipid lower drug-HMG Co-A reductase inhibitors. Because atorvastatin and everolimus have metabolism via Cytochrome P450 subfamily 3A4 both, so investigator made the hypothesis that when patients received everolimus with atorvastatin will change area under the time concentration curve of everolimus.

Detailed Description
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Population : Thai postrenal transplantation recipient who received everolimus and have hypercholesterolemia in posttransplantation clinic at Faculty of Medicine, Chulalongkorn University. Study Design : Experimental study, Two-sample crossover study Sample size calculation :N = 18 Primary outcome : 12-hour area under the time concentration curve of everolimus Secondary outcome : renal function (serum creatinine, creatinine clearance) Method : Patients will random to everolimus or everolimus with atorvastatin 20 mg arm for 1 month. Take blood sample for everolimus concentration at time 0,0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 hour After first blood sample, patients will received everolimus only for 1 month (wash out period) Patients will switch to another arm eg.patient who had received everolimus will switch to everolimus with atorvastatin 20 mg for 1 month Take blood sample for everolimus concentration at time 0,0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 hour Everolimus level will analyse for 12-hour AUC of everolimus.

Official Title
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Drug Interaction and Pharmacokinetic Assessment of Everolimus When Coadministered With Atorvastatin in Renal Transplantation Recipient

Conditions
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Difference of 12-hour AUC

Intervention / Treatment
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* Drug: Atorvastatin 20 mg
* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post renal transplantation recipient who received immunosuppressive drug Everolimus and has hypercholesterolemia Co everolimus level within 3-12 ng/mL Informed consent Patient can follow research methodology Exclusion Criteria: Patient don't want to participate in the study Post renal transplantation recipient who have normal lipid profile

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: everolimus<br>Everolimus administration with adjusted dose to target C trough (C0) level between 3-12 ng/mL | Drug: Atorvastatin 20 mg<br>* Add atorvastatin 20 mg and compare 12-hour AUC of everolimus between Arm everolimus and everolimus with atorvastatin 20 mg<br>* Other names: Lipitor 20 mg;|
| Experimental: everolimus with atorvastatin 20 mg<br>Co-administration of everolimus and atorvastatin. Everolimus administration with adjusted dose to target C trough (C0)level between 3-12 ng/mL. Atorvastatin 20 mg/day (fixed dose) | Drug: Everolimus<br>* Administration only everolimus, no atorvastatin. Everolimus administration with adjusted dose to target C trough (C0)level between 3-12 ng/mL.<br>* Other names: Everolimus alone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-hour area under the time concentration curve of everolimus | compare when taking only everolimus to coadministered with atorvastatin | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal function | Renal function : serum creatinine, 24 hour creatinine clearance 24 hour urine protein, Urinalysis Sample take at month 0,1,2,3 | 3 months | 
| Liver function test | Total protein, Albumin, total bilirubin, direct bilirubin, AST, ALT, Alkaline phosphatase at month 0,1,2,3 | 3 month | 
| Lipid profile | Total cholesterol, Triglyceride, HDL, LDL at month 0,1,2,3 | 3 month | 
| Rhabdomyolysis | Adverse drug reaction from atorvastatin by measured CPK at month 0,1,2,3 | 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Interaction, Pharmacokinetics, Everolimus, Atorvastatin