Stavudine Lamivudine

Pharmacology Abacavir is a synthetic carbocyclic synthetic nucleoside analog with inhibitory activity against HIV. Abacavir has synergistic activity in combination with amprenavir, nevirapine, and zidovudine and additive activity in combination with didanosine, lamivudine, stavudine, and zalcitabine in vitro. 

As a class effect NRTIs are associated with lactic acidosis and hepatic steatosis, conditions which may occur more frequently in pregnant women. The individual NRTIs have their own adverse reactions. Pancreatitis is seen with lamivudine, stavudine, di-danosine and rarely with zalcitabine while the latter three agents can also induce peripheral neuropathy. 

Nevirapine = Viramune] (dipyridodiazepinone) [NRTIs in clinical use Abacavir (ABC) Adefovir dipivoxil (9-[2-Phosphonomethoxy)ethyl] -adenine PMEA) AZT Didanosine (= 2, 3 -Dideoxyinosine) Lamivudine Stavudine Zalcitabine (2, 3 -Dideoxycytidine]... 

A 44-year-old HIV-1 infected woman from the Ivory Coast, who was taking stavudine, lamivudine, efavirenz, and pyrimethamine plus sulfadiazine for Toxoplasma encephalitis, developed a maculopapular rash on both arms. The sulfadiazine was withdrawn and clindamycin was added. Ten days later her condition had worsened. Her temperature was 40 C, pulse rate 137/minute, and respiratory rate 26/minute. She had a generalized maculopapular rash without mucosal involvement, moderate abdominal tenderness, hepatomegaly, jaundice, and bilateral crackles. Her white cell count was 16 x 10 /1 with 9% eosinophils and 51% lymphocytes. A chest X-ray showed moderate bilateral interstitial pneumonitis. All drugs were withdrawn and she was given intravenous methylprednisolone. The skin rash and aU systemic manifestations resolved within 1 week and HIV treatment was restarted uneventfully with lamivudine, stavudine, and nehinavir. 

Adverse effects Didanosine Lamivudine Stavudine Zalcitabine Zidovudine... 

Pancreatitis has been observed in patients treated with didanosine, lamivudine, stavudine, and zalcitabine (29), but its incidence is also increased in drug-naive patients with advanced HIV infection (30). 

Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of medications approved for the management of HIV infection. They are structural analogues of nucleic acids. They undergo intracellular phosphorylation to a triphosphate metabolite and it is this metabolite that is pharmacologically active against reverse transcriptase. Drugs in this class include abacavir, adefovir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine. 

B. Fan, M.G. Bartlett, J.T. Stewart, Determination of lamivudine, stavudine and efavirenz in human serum using LC-ESI-MS-MS with ionization polarity switch, Biomed. Chromatogr., 16 (2002) 383. 

Lamivudine -I- Stavudine Lamivudine -I- Zidovudine Lamivudine + Stavudine + Efavirenz Lamivudine -I- Stavudine + Nevirapine Lamivudine -I- Zidovudine + Efavirenz Lamivudine -I- Zidovudine + Nevirapine Lamivudine -I- Zidovudine + Abacavir Tenofovir -I- Emtricitabine... 

Lamivudine + Stavudine + Nevirapine Lamivudine + Zidovudine + Nevirapine Lamivudine + Zidovudine + Abacavir... 

Inhibit viral reverse transcriptase Zidovudine, didanosine, zalcitabine, lamivudine, stavudine, nevirapine... 

Parameter Zidovudine Lamivudine Stavudine Didanosine Abacavir Zalcitabine Tenofovir Emtricitabine... 

Anti-HIV drugs Nucleoside reverse transcriptase inhibitors Zidovudine Didanosine, lamivudine, stavudine, zalcitabine... 

NRTIs are water soluble, and are mainly eliminated by the kidneys (di-danosine, lamivudine, stavudine, and zalcitabine) or undergo hepatie glu-curonidation (abacavir, zidovudine). The few important interactions with these drugs primarily involve altered renal clearance. For zidovudine (and possibly abacavir) some interactions occur via altered glucuronidation, but the clinical relevance of these are less clear (e.g. rifampicin , (p.792)). Cytochrome P450-mediated interactions are not important for this class of drugs. 

Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Zalcitabine, Zidovudine Tenofovir... 

Established interactions. With the NRTTs that are actively excreted via the kidneys (e.g. lamivudine, stavudine, and zaicitabine), it is unlikely that dosage alterations are necessary unless the patient has renal impairment. However, when both drugs are needed, patients should be closely monitored for signs of toxicity. Moreover, the UK manufacturer of lamivudine recommends that the use of lamivudine with high-dose co-trimoxazole for the treatment of Pneumocystis pneumonia and toxoplasmosis should be avoided. Since renal clearance represents only 20 to 30% of the total clearance of zidovudine, the authors of two of these reports " suggest that this interaction is unlikely to be clinically important for zidovudine unless the glucuronidation by the liver is impaired by liver disease or other drugs. Didanosine also does not appear to interact to a clinically relevant extent. 

Combination of 16 ARVs seven HIV protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfmavir, ritonavir, and saquinavir), seven nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, and zidovudine), and two nonnucleoside reverse transcriptase inhibitors (efavirenz and nevirapine)... 

Aymard, G. Legrand, M. Trichereau, N. Diquet, B. Determination of twelve antiretroviral agents in human plasma sample using reversed-phase high-performance liquid chromatography, J.Chromatogr.B, 2000, 744, 227-240. [for amprenavir efavirenz indinavir nelflnavir ritonavir saquinavir abacavir didanosine lamivudine stavudine nevirapine zidovudine]... 

Fan, B. Bartlett, M.G. Stewart, J.T. Determination of lamivudine/stavudine/efavirenz in human serum using liquid chromatography/electrospray tandem mass spectrometry with ionization polarity switch, Biomed.Chromatogr., 2002, 16, 383-389. [aprobarbital is internal standard SPE]... 

Simon, VA. Thiam, M.D. Lipford, L.C. Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance hquid chromatography, J.ChromatogrA, 2001,913,447-453. [zalcitabine lamivudine stavudine didanosine zidovudine nevirapine abacavir indinavir delavirdine nelfinavir saquinavir ritonavir efavirenz]... 

Moyer, T.P. Temesgen, Z. Enger, R. Estes, L. Charlson, J. OUver, L. Wight, A. Drug monitoring of antiretroviral therapy for HIV-1 infection method vaUdation and results of a pilot study, CUn.Chem., 1999, 45, 1465-1476. [SPE LOQ 100 ng/mL for lamivudine didanosine lamivudine stavudine zalcitabine zidovudine delavirdine nevirapine indinavir nelflnavir ritonavir saquinavir]... 

SPE LOD 260 ng/mL for lamivudine zalcitabine lamivudine stavudine didanosine zidovudine nevirapine abacavir indinavir deiavirdine nelimavir saquinavir ritonavir efavirenz] Solas, C. Li, Y.-F. Xie, M.-Y. Sommadossi, J.-P. Zhou, X.-J. Intracellular nucleotides of (-)-2, 3 -deoxy-3 -thiacytidine in peripheral blood mononuclear cells of a patient infected with human immunodeficiency virus, Aratimicro6..4 erats Chemother., 1998, 42, 2989-2995. 

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