those shown below. Asthenia, malaise Diarrhea Nausea and vomiting Abdominal pain Dizziness Insomnia Kidney failure Sweating Taste abnormality Metabolic effects, including Hypercholesterolemia Hypertriglyceridemia Elevated transaminases Elevated creatine kinase Adverse drug reactions Ritonavir exhibits hepatic activity. It induces CYP1A2 and inhibits the major P450 isoforms 3A4 and 2D6. Concomitant therapy of ritonavir with a variety of medications may result in serious and sometimes fatal drug interactions. Due to it being a strong inhibitor (that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance) of both Cytochrome P450 enzymes CYP2D6 and CYP3A4, ritonavir can severely potentiate and prolong the half-life and/or increase the blood concentration of phenobarbital, primidone, carbamazepine, phenytoin, PDE5 inhibitors like sildenafil, opioids such as hydrocodone, oxycodone, pethidine and fentanyl, antiarrhythmic agents such as amiodarone, propafenone and disopyramide, Immunosuppressants such as tacrolimus, voclosporin and sirolimus, neuroleptics like clozapine, lurasidone and pimozide, as well as some chemotherapeutic agents, benzodiazepines and some ergot derivatives Pharmacology Pharmacodynamics Ritonavir was originally developed as an inhibitor of HIV protease, one of a family of pseudo-C-symmetric small molecule inhibitors. Ritonavir is rarely used for its own antiviral activity but remains widely used as a booster of other protease inhibitors. More specifically, ritonavir is used to inhibit a particular enzyme, in intestines, liver, and elsewhere, that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4). The drug binds to and inhibits CYP3A4, so a low dose can be used to enhance other protease inhibitors. This discovery drastically reduced the adverse effects and improved the efficacy of protease inhibitors and HAART. However, because of the general role of CYP3A4 in xenobiotic metabolism, dosing with ritonavir also affects the efficacy of numerous other medications, adding to the challenge of prescribing drugs concurrently. Pharmacokinetics The capsules of the medication do not have the same bioavailability as the tablets. Ritonavir was demonstrated to have an in vitro potency of EC50=0.02µM and highly sustained concentration in plasma after oral administration in several species. Chemistry Ritonavir was initially derived from a moderately potent and orally bioavailable small molecule, A-80987. The P3 and P2′ heterocyclic groups of A-80987 were redesigned to create an analogue, now known as ritonavir, with improved pharmacokinetic properties to the original. Full details of the synthesis of ritonavir were first published by scientists from Abbott Laboratories. In the first step shown, an aldehyde derived from phenylalanine is treated with zinc dust in the