(E)-14,17,26,32-tetrabutyl-5-ethyl-8-(1-hydroxy-2-methylhex-4-enyl)-1,3,9,12,15,18,20,23,27-nonamethyl-11,29-dipropyl-1,3,6,9,12,15,18,21,24,27,30-undecaazacyclodotriacontan-2,4,7,10,13,16,19,22,25,28,31-undecaone

Absorption
Oral
Absorption is incomplete and variable. Bioavailability is less than 10% in liver transplant patients ( Sandimmune ), up to 89% in renal transplant patients ( Sandimmune ), and about 30% for the oral solution. Tmax is 1.5 to 2 h ( Gengraf and Neoral ) and 3.5 h ( Sandimmune ). Food decreases the AUC and C max .

Distribution
Vd is 3 to 5 L/kg at steady state (IV). Cyclosporine is 90% protein bound (primarily lipoprotein) and is excreted in human milk.

Metabolism
Extensively metabolized by CYP3A in the liver and to a lesser degree in the GI tract and kidney.

Elimination
Eliminated primarily in the bile; 6% is excreted unchanged in the urine (0.1% as unchanged drug). The t½ is about 8.4 h ( Gengraf and Neoral ) and about 19 h ( Sandimmune ). Blood Cl is about 5 to 7 mL/min/kg (IV).

Allopurinol, amiodarone, beta-blockers (eg, carvedilol), bromocriptine, colchicine, danazol, diltiazem, fluconazole, grapefruit and grapefruit juice, imipenem-cilastatin, itraconazole, ketoconazole, macrolide antibiotics (eg, erythromycin), metoclopramide, nefazodone, nicardipine, protease inhibitors (eg, indinavir, nelfinavir, ritonavir, saquinavir), quinupristin/dalfopristin, serotonin reuptake inhibitors (eg, fluoxetine, sertraline), verapamil
May increase cyclosporine concentrations.

Aminoglycosides, amphotericin B, cimetidine, colchicine, NSAIDs, ranitidine, tacrolimus, trimethoprim-sulfamethoxazole, melphalan, quinolones
Additive nephrotoxicity possible.

Azathioprine, corticosteroids, cyclophosphamide, verapamil
May cause additive immunosuppression, increasing risk of infection and malignancy.

Carbamazepine, hydantoins, nafcillin, octreotide, orlistat, phenobarbital, rifampin, rifabutin, St. John's wort, terbinafine, ticlopidine
May decrease cyclosporine effects.

Digoxin, methotrexate, sirolimus
Plasma levels of these agents may be elevated by cyclosporine.

Etoposide
May increase etoposide concentrations.

Live vaccines
Vaccination may be less effective.

Metoclopramide
Increases absorption of cyclosporine.

Potassium-sparing diuretics
Causes hyperkalemic effects; avoid concomitant use.

Statins (eg, lovastatin)
May cause severe myopathy or rhabdomyolysis; avoid concurrent use.