Difference of 12-hour AUC
Conditions
Keywords
Drug Interaction, Pharmacokinetics, Everolimus, Atorvastatin
Brief summary
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
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 : 1. Patients will random to everolimus or everolimus with atorvastatin 20 mg arm for 1 month. 2. Take blood sample for everolimus concentration at time 0,0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 hour 3. After first blood sample, patients will received everolimus only for 1 month (wash out period) 4. Patients will switch to another arm eg.patient who had received everolimus will switch to everolimus with atorvastatin 20 mg for 1 month 5. Take blood sample for everolimus concentration at time 0,0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 hour 6. Everolimus level will analyse for 12-hour AUC of everolimus.
Interventions
Add atorvastatin 20 mg and compare 12-hour AUC of everolimus between Arm everolimus and everolimus with atorvastatin 20 mg
DRUGEverolimus
Administration only everolimus, no atorvastatin. Everolimus administration with adjusted dose to target C trough (C0)level between 3-12 ng/mL.
Sponsors
Ratchadapiseksompotch Research Fund
Chulalongkorn University
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-hour area under the time concentration curve of everolimus | 3 months | compare when taking only everolimus to coadministered with atorvastatin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal function | 3 months | Renal function : serum creatinine, 24 hour creatinine clearance 24 hour urine protein, Urinalysis Sample take at month 0,1,2,3 |
| Liver function test | 3 month | Total protein, Albumin, total bilirubin, direct bilirubin, AST, ALT, Alkaline phosphatase at month 0,1,2,3 |
| Lipid profile | 3 month | Total cholesterol, Triglyceride, HDL, LDL at month 0,1,2,3 |
| Rhabdomyolysis | 3 month | Adverse drug reaction from atorvastatin by measured CPK at month 0,1,2,3 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation of 12-hour AUC and point of everolimus level | 3 months | To correlate between 12-hour AUC and point of everolimus level |
Countries
Thailand
Outcome results
None listed