Drug Breakdown: SIROLIMUS

Day 1: A streptomyces soil isolate from Easter Island (correct name Rapa Nui) found in the 1960s, the generic name for #rapamycin is #sirolimus. It is a macrolide compound with immune suppressive, antitumour & antifungal properties

Day 2: #sirolimus tablet or oral solution are licensed for the prevention of kidney organ rejection in adults. 6 mg loading dose day 1, then 2 mg x1/day maintenance. Used as ongoing treatment combined with ciclosporin & corticosteroids initially, then continued alone after 2–3 months & ciclosporin wash out

Day 3: #sirolimus kinetics; bioavailability is better for tablet compared to the oral solution. Metabolism via phase 2 demethylation & hydroxylation in gut/liver >inactive metabolites. Faecal elimination. Elimination mean t½ 62hrs. Substrate for CYP3A4 & P-gp, so potential for drug drug interactions. #sirolimus has a narrow therapeutic index; requires therapeutic monitoring with dose adjusted according to trough concentration. Safety monitoring periodically throughout treatment

Day 4: #sirolimus is a potent inhibitor of T & B lymphocytes; it forms a complex with intracellular protein FKB12. This blocks the protein kinase TOR (target of rapamycin) & halts cell division. Differs from cousin drug #tacrolimus which ↓ T-cell activation by blocking calcineurin