Abstract
Sixty-six renal transplant patients maintained on Sandimmune®, the traditional formulation of cyclosporine, participated in an open-label, sequential trial to compare intrapatient variability in drug exposure before and after a switch to Neoral®. Three 12-hour cyclosporine pharmacokinetic profiles were obtained over approximately 6 weeks while patients were receiving Sandimmune. Patients were then switched to Neoral, with the dose adjusted as necessary to maintain target trough blood cyclosporine concentrations. At approximately 4 and 6 weeks postconversion, 2 additional pharmacokinetic profiles were obtained. Key pharmacokinetic variables analyzed were area under the concentration-time curve (AUC), maximum concentration (C(max)), and predose trough concentration (C0). Intrapatient variability in drug exposure for dose-normalized mean AUC, C(max), and C0 was significantly reduced with Neoral, with 50 (76%), 57 (86%), and 45 (68%) patients experiencing reduced variability in AUC, C(max) and C0, respectively (P <0.001). Additionally, the total exposure to cyclosporine was more predictable from the trough level of cyclosporine with Neoral; the relationship between AUC and C0 was 0.81 for Neoral at both pharmacokinetic profiling time points but ranged from 0.49 to 0.69 for the 3 Sandimmune time points. The large reductions in intrapatient variability of pharmacokinetic variables for cyclosporine provided by Neoral indicate an improvement in the consistency of drug exposure, which may translate into important clinical benefits.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 160-171 |
| Number of pages | 12 |
| Journal | Clinical Therapeutics |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1999 |
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Keywords
- Bioavailability
- Cyclosporine
- Pharmacokinetics
- Transplant
ASJC Scopus subject areas
- Pharmacology
Cite this
Reduced intrapatient variability of cyclosporine pharmacokinetics in renal transplant recipients switched from oral Sandimmune to Neoral. / Mendez, Robert; Abboud, Hanna; Burdick, James F.; Copley, Brian; Freeman, Richard; Batiuk, Thomas D.; Cooney, Gerard F.; Barbeito, Ralph.
In: Clinical Therapeutics, Vol. 21, No. 1, 1999, p. 160-171.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduced intrapatient variability of cyclosporine pharmacokinetics in renal transplant recipients switched from oral Sandimmune to Neoral
AU - Mendez, Robert
AU - Abboud, Hanna
AU - Burdick, James F.
AU - Copley, Brian
AU - Freeman, Richard
AU - Batiuk, Thomas D.
AU - Cooney, Gerard F.
AU - Barbeito, Ralph
PY - 1999
Y1 - 1999
N2 - Sixty-six renal transplant patients maintained on Sandimmune®, the traditional formulation of cyclosporine, participated in an open-label, sequential trial to compare intrapatient variability in drug exposure before and after a switch to Neoral®. Three 12-hour cyclosporine pharmacokinetic profiles were obtained over approximately 6 weeks while patients were receiving Sandimmune. Patients were then switched to Neoral, with the dose adjusted as necessary to maintain target trough blood cyclosporine concentrations. At approximately 4 and 6 weeks postconversion, 2 additional pharmacokinetic profiles were obtained. Key pharmacokinetic variables analyzed were area under the concentration-time curve (AUC), maximum concentration (C(max)), and predose trough concentration (C0). Intrapatient variability in drug exposure for dose-normalized mean AUC, C(max), and C0 was significantly reduced with Neoral, with 50 (76%), 57 (86%), and 45 (68%) patients experiencing reduced variability in AUC, C(max) and C0, respectively (P <0.001). Additionally, the total exposure to cyclosporine was more predictable from the trough level of cyclosporine with Neoral; the relationship between AUC and C0 was 0.81 for Neoral at both pharmacokinetic profiling time points but ranged from 0.49 to 0.69 for the 3 Sandimmune time points. The large reductions in intrapatient variability of pharmacokinetic variables for cyclosporine provided by Neoral indicate an improvement in the consistency of drug exposure, which may translate into important clinical benefits.
AB - Sixty-six renal transplant patients maintained on Sandimmune®, the traditional formulation of cyclosporine, participated in an open-label, sequential trial to compare intrapatient variability in drug exposure before and after a switch to Neoral®. Three 12-hour cyclosporine pharmacokinetic profiles were obtained over approximately 6 weeks while patients were receiving Sandimmune. Patients were then switched to Neoral, with the dose adjusted as necessary to maintain target trough blood cyclosporine concentrations. At approximately 4 and 6 weeks postconversion, 2 additional pharmacokinetic profiles were obtained. Key pharmacokinetic variables analyzed were area under the concentration-time curve (AUC), maximum concentration (C(max)), and predose trough concentration (C0). Intrapatient variability in drug exposure for dose-normalized mean AUC, C(max), and C0 was significantly reduced with Neoral, with 50 (76%), 57 (86%), and 45 (68%) patients experiencing reduced variability in AUC, C(max) and C0, respectively (P <0.001). Additionally, the total exposure to cyclosporine was more predictable from the trough level of cyclosporine with Neoral; the relationship between AUC and C0 was 0.81 for Neoral at both pharmacokinetic profiling time points but ranged from 0.49 to 0.69 for the 3 Sandimmune time points. The large reductions in intrapatient variability of pharmacokinetic variables for cyclosporine provided by Neoral indicate an improvement in the consistency of drug exposure, which may translate into important clinical benefits.
KW - Bioavailability
KW - Cyclosporine
KW - Pharmacokinetics
KW - Transplant
UR - http://www.scopus.com/inward/record.url?scp=0033048295&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033048295&partnerID=8YFLogxK
U2 - 10.1016/S0149-2918(00)88276-4
DO - 10.1016/S0149-2918(00)88276-4
M3 - Article
C2 - 10090433
AN - SCOPUS:0033048295
VL - 21
SP - 160
EP - 171
JO - Clinical Therapeutics
JF - Clinical Therapeutics
SN - 0149-2918
IS - 1
ER -