4. Marketed formulations: KALETRAfilm-coated tablets are available in two strengths: 200 mg of lopinavir and 50 mg of ritonavir 100 mg of lopinavir and 25 mg of ritonavir. KALETRAoral solution contains 42.4% alcohol (v/v).
5. Pharmacokinetics Absolute bioavailability is unknown due to lack of an adequate I.V formulation Protein binding : 98-99% Metabolism: metabolized by the hepatic cytochrome P450 system, exclusively by the CYP3A isozyme. Elimination : <3% excreted unchanged in urine T1/2= 2-3 hrs on single administration 4-6 hrs on multiple dose administration
6. Ritonavir (RIT/Norvir) Toxicity Hepatotoxicity Hyperlipidemia Hyperglycemia/ insulin resistance Drug-drug interactions! Potent inhibition CYP3A4 Increases levels of other PIs Side Effects GI Nausea/vomiting Diarrhea Abdominal pain Dosing “boosting” 100-200mg qd
7. KAL (lopinavir +ritonavir/Kaletra) Toxicity Hyperlipidemia Hyperglycemia/ insulin resistance Drug-drug interactions Side Effects GI Nausea/vomiting Diarrhea Abdominal pain
9. Drug-drug Interactions of Norvir® & Kaletra® lopinavir/ritonavir (Kaletra®) , is the only combination PI, having ritonavir (Norvir®) as one of its components Ritonavir (Norvir®) is the most potential for clinically significant psychotropic drug interactions Ritonavir is a potent cytochrome P450 3A4, 2D6, 2C9, 2C19, 2A6, 1A2 & 2E1 inhibitor As with antipsychotic medications, when combining Norvir® or Kaletra® with psychotropics, it is safer to start low dose
17. Principle Foreign body granulomas were provoked in rats by subcutaneous implantation of pellets of compressed cotton. After several days, histologically giant cells and undifferentiated connective tissue can be observed.
19. Procedure Weigh the rats & divide them into two groups (control &treatment) Anaesthetize with Diethyl ether The back skin is shaved & disinfect with 70% ethanol An incision is made in lumbar region Sterilized cotton pellet is placed in scapular region The animals are treated 7 days Remove the pellets & dried until the weight remain constant Measure the weight of granuloma by substracting the initial cotton pellet weight.