Lopinavir
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Lopinavir
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| Systematic (IUPAC) name | |
| (2S)-N-[(2S,4S,5S)-5-{[2-(2,6-dimethylphenoxy) acetyl]amino}-4-hydroxy-1,6-diphenyl-hexan-2-yl]- 3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide |
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| Identifiers | |
| CAS number | 192725-17-0 |
| ATC code | J05AE06 |
| PubChem | 92727 |
| DrugBank | EXPT00388 |
| Chemical data | |
| Formula | C37H48N4O5 |
| Mol. weight | 628.810 g/mol |
| Pharmacokinetic data | |
| Bioavailability | Unknown |
| Protein binding | 98-99% |
| Metabolism | Hepatic |
| Half life | 5 to 6 hours |
| Excretion | Mostly fecal |
| Therapeutic considerations | |
| Pregnancy cat. |
C (U.S.) |
| Legal status | |
| Routes | Oral |
Lopinavir (ABT-378) is an antiretroviral of the protease inhibitor class. It is marketed by Abbott as Kaletra®, a co-formulation with a sub-therapeutic dose of ritonavir, as a component of combination therapy to treat HIV/AIDS.
As of 2006, lopinavir/ritonavir forms part of the preferred combination for first-line therapy recommended by the US DHHS.[1] It is available as capsules, tablets and oral solution.
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[edit] History
Lopinavir was developed by Abbott in an attempt to improve on the HIV resistance and serum protein-binding properties of the company's earlier protease inhibitor, ritonavir.[2] Administered alone, lopinavir has insufficient bioavailability; however, like several HIV protease inhibitors, its blood levels are greatly increased by low doses of ritonavir, a potent inhibitor of cytochrome P450 3A4.[2] Abbott therefore pursued a strategy of co-administering lopinavir with sub-therapeutic doses of ritonavir, and lopinavir is only marketed as a co-formulation with ritonavir. It is the first multi-drug capsule to contain a drug not available individually.
Lopinavir/ritonavir was approved by the US FDA on 15 September 2000, and in Europe in April 2001. Its patent will expire in the US on June 26, 2016.
[edit] Pharmacology
Lopinavir is highly bound to plasma proteins (98-99%).[3]
There are contradictory reports regarding lopinavir penetration into the CSF. Anecdotal reports state that lopinavir cannot be detected in the CSF; however, a study of paired CSF-plasma samples from 26 patients receiving lopinavir/ritonavir found lopinavir CSF levels above the IC50 in 77% of samples.[4]
[edit] Adverse effects
The most common adverse effects observed with lopinavir/ritonavir are diarrhoea and nausea. In key clinical trials, moderate or severe diarrhoea occurred in up to 27% of patients, and moderate/severe nausea in up to 16%.[3] Other common adverse effects include abdominal pain, asthenia, headache, vomiting and, particularly in children, rash.[3]
Raised liver enzymes and hyperlipidemia (both hypertriglyceridemia and hypercholesterolemia) are also commonly observed during lopinavir/ritonavir treatment.
[edit] References
- ^ DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download from AIDSInfo)
- ^ a b Sham HL, Kempf DJ, Molla A, et al. (1998) ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob. Agents Chemother. 42: 3218-24
- ^ a b c KALETRA® (lopinavir/ritonavir) capsules; (lopinavir/ritonavir) oral solution. Prescribing information. April 2005
- ^ Capparelli E, Holland D, Okamoto C, et al. (2005). "Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV". AIDS (London, England) 19 (9).
[edit] External link
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