Guidelines to Antiretroviral Drug Therapy in Kenya: CHAPTER THREE: PHARMACOTHERAPEUTICS OF ARVS: 3.2 Pharmacokinetic properties of Antiretrovirals

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	Guidelines to Antiretroviral Drug Therapy in Kenya (WHO; 2001; 78 pages)
		FOREWORD
		ACKNOWLEDGMENT
		CHAPTER ONE: INITIATING ANTIRETROVIRAL THERAPY
			1.1 Introduction
			1.2 Guidelines to making a diagnosis of HIV infection
			1.3 Laboratory Diagnosis of HIV infection
			1.4 Goals of therapy
			1.5 When to start therapy
			1.6 Risks and benefits of delayed initiation of therapy and of early therapy in the Asymptomatic HIV-Infected Patient
			1.7 Antiretroviral profile
			1.8 What drug combination to start with?
		CHAPTER TWO: MONITORING AND CHANGING THERAPY
			2.1 Surrogate markers
			2.2 Resistance testing
			2.3 How often should CD4 Cell Count and Viral Load be performed (Frequency)
			2.4 Treatment failure
			2.5 Reasons for non-adherence
			2.6 Considerations for changing a failing regimen
			2.7 Guidelines for changing an antiretroviral regimen for suspected drug failure
			2.8 Potential options for changing therapy*
		CHAPTER THREE: PHARMACOTHERAPEUTICS OF ARVS
			3.1 Characteristics of available antiretroviral drugs
			3.2 Pharmacokinetic properties of Antiretrovirals
		CHAPTER FOUR: GUIDELINES FOR THE USE OF ANTIRETROVIRAL DRUGS IN PAEDIATRIC HIV INFECTION
			4.1 Overview
			4.2 Diagnosis of HIV infection in children
			4.3 When to initiate treatment
			4.4 Initiation of treatment
			4.5 Agents to choose for initial treatment
			4.6 Dosages for paediatric formulations
			4.8 Monitoring
			4.9 When to change therapy
		CHAPTER FIVE: MANAGEMENT OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTED PREGNANT WOMEN AND PREVENTION OF MOTHER TO CHILD TRANSMISSION (MTCT) OF HIV
			5.1 Overview
			5.2 Factors affecting mother to child transmission
			5.3 Outline antenatal, intrapartum postpartum and postnatal care
			5.4 Antiretroviral Therapy to prevent MTCT
		CHAPTER SIX: SPECIAL CONSIDERATIONS
			6.1 Acute retroviral syndrome (ARVS)
			6.2 ARV drugs and the treatment of Tuberculosis
			6.3 Immune recovery syndrome
		CHAPTER SEVEN: WHEN TO STOP TREATMENT (INTERRUPTIONS)
			7.1 Structured treatment interruptions (STI's)
			7.2 Non structured treatment interruption
		CHAPTER EIGHT: GUIDELINES FOR POST EXPOSURE PROPHYLAXIS
			8.1 Treatment of exposure sites
			8.2 Timing of post - HIV exposure prophylaxis initiation
			8.3 Assessment of exposure risk
			8.4 Post - HIV exposure prophylaxis
			8.5 Recommended HIV serology after exposure
			8.6 Management of health care workers with accidental exposure to HIV infection
			8.7 Management of hospital staff with sharp injury or exposure to blood and body fluids
			8.8 Management of non occupational exposure to HIV infection
			8.9 Management of non-sexual and non occupational Exposures to HIV
		CHAPTER NINE: ACCESS TO DRUGS IN KENYA
		APPENDICES
			I. Drug to drug interactions
			II. Drug to drug interactions (continued)
			III. Drug Interactions Between Antiretrovirals and Other Drugs
			IV. Nucleoside Reverse Transcriptase Inhibitors (NRTIS)
			V. Drug Interactions: Protease Inhibitors
			VI. Drug Interactions: Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors - Cont.
			VII. Drug That Should Not be Used With Antiretrovirals
			VIII. Drugs that should not be used with Protease Inhibitors Antiretrovirals
			IX. HIV-related drugs with overlapping toxicities
			X. Anti-retroviral therapy for preventing MTCT
		BACK COVER

3.2 Pharmacokinetic properties of Antiretrovirals

Drug	Oral Bioavailability	Serum Half-life	Intracellular Half-life	Elimination
Zidovudine (AZT, ZDV) Retrovir	60%	1.1 hours	3 hours	Metabolized to AZT glucoronide (GAZT) Renal excretion of GAZT
Didanosine (ddl) Videx	30-40%	1.6 hours	25-40 hours	Renal excretion 50%
Zalcitabine (ddc) Hivid.	85%	1.2 hours	3 hours	Renal excretion 70%
Stavudine (d4T) Zerit	86%	1.0 hours	3.5 hours	Renal excretion 50%
Lamivudine (3TC) Epivir	86%	3-6 hours	12 hours	Renal excretion unchanged
Abacavir (ABC) Ziagen	83%	1.5 hours	3.3 hours	Metabolized by alcohol dehydrogenate and glucoronyl transferase. Renal excretion of metabolites 82%
Nevirapine Viramune	>90%	25-30 hours	Data not available	Metabolized by cytochrome P450 (3A inducer); 80% excreted in urine (glucoronidated metabolites, <5% unchanged), 10% in faeces.
Efavirenz Stocrin,	Data not available	40-55 hours	Data not available	Metabolized by cytochrome P450 (3A mixed inducer/ inhibitor); 14-34% excreted in urine (glucoronidated metabolites, <1% unchanged), 16-61 % in faeces.

Drug	Oral Bioavailability	Serum Half-life	Metabolism
Indinavir (Crixivan)	65%	1.5-2 hours	Cytochrome P450 3A4 inhibitor (less than Ritonavir)
Ritonavir (Norvir)	Not determined	3-5 hours	Cytochrome P45U Potent 3A4 inhibitor
Nelfinavir (Viracept)	20-80%	3.5-5 hours	Cytochrome P450 3A4 inhibitor (less than Ritonavir)
Saquinavir, hard gel formulation (Invirase)	4% but is erratic	1-2 hours	Cytochrome P450 3A4 inhibitor (less than Ritonavir)
Saquinavir, soft gel formulation (Fortovase)	Not determined	1-2 hours	Cytochrome P450 3A4 inhibitor (less than Ritonavir)
Amprenavir (Agenerase)	Not determined	7.1-10.6 hours	Cytochrome P450 3A4 inhibitor
Lopinavir + Ritonavir (Kelatra)	Not determined	5-6 hours	Cytochrome P450 3A4 inhibitor

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