[[Image:Drug metabolism1.jpg|right|370 px|Drug metabolism]]
==Introduction==
[[Image:Drug metabolism1.jpg|right|250 px|Drug metabolism]]
Drug metabolism is a detoxification function the human body possesses to defend itself from environment hostility.
Ideally, a drug should reach the site of action intact, cure the disease, and leave the body after it completes its mission.
[[Image:struc.jpg|center|thumb|300px|'''Chemical Structure of GW844520''']]
Plasmodium falciparum is the species of malaria parasite that predominates in Africa and is the cause of most of the mortality from malaria worldwide. Effective treatment options are often restricted due to drug resistance, particularly for P. falciparum. There is an immediate need to develop novel anti-malarial agents that provide rapid and effective treatment.GW844520 is fully active against isolates carrying resistance determinants to marketed agents and shows no cross-resistance with agents in current use, including atovaquone.
'''Models/Species:'''Male CD1 mouse, male Sprague-Dawley rat, male beagle dog, male cynomolgus monkey and mixed gender human liver microsomes.
===Test Results===
{|border="2" cellspacing="0" cellpadding="4" width="72%"
|align = "center" bgcolor = "#C2D69A" colspan = "7"|'''Pharmacokinetics of GW844520 After Oral Administration to Mouse, Rat, Dog, and Monkey'''
|-
|align = "center" bgcolor = "#8DB4E3"|'''Species'''
|align = "center" bgcolor = "#8DB4E3"|'''Dose (mg/kg)'''
|align = "center" bgcolor = "#8DB4E3"|'''Cmax (µg/mL)'''
|align = "center" bgcolor = "#8DB4E3"|'''Tmax (h)'''
|align = "center" bgcolor = "#8DB4E3"|'''AUC0- (µg h/mL)'''
|align = "center" bgcolor = "#8DB4E3"|'''T1/2 h'''
|align = "center" bgcolor = "#8DB4E3"|'''F (%)'''
|-
|align = "center"|'''Mouse'''
|align = "center"|0.5
|align = "center"|0.28
|align = "center"|4
|align = "center"|8.54
|align = "center"|23.6
|align = "center"|72
|-
|align = "center"|'''Rat'''
|align = "center"|0.5
|align = "center"|0.25 ± 0.02
|align = "center"|2 (1-2)
|align = "center"|4.14 ± 0.96
|align = "center"|7.1 ± 1.7a
|align = "center"|118
|-
|align = "center"|'''Dog'''
|align = "center"|0.4
|align = "center"|0.14 ± 0.02
|align = "center"|24 (4-24)
|align = "center"|22.8 ± 7.9
|align = "center"|214 ± 30
|align = "center"|51 ± 11
|-
|align = "center"|'''Monkey'''
|align = "center"|0.4
|align = "center"|0.12 ± 0.01
|align = "center"|4 (4-8)
|align = "center"|13.5 ± 0.6
|align = "center"|88.4 ± 4.4
|align = "center"|69 ± 6
|}
{|border="2" cellspacing="0" cellpadding="4" width="36%"
|align = "center" bgcolor = "#C2D69A" colspan = "3"|'''In Vitro Cell Partitioning of GW844520 in Animal and Human Blood'''
|-
|align = "center" bgcolor = "#8DB4E3"|'''Species'''
|align = "center" bgcolor = "#8DB4E3"|'''Concentration (µg/mL)'''
|align = "center" bgcolor = "#8DB4E3"|'''Blood to plasma ratio'''
|-
|align = "center" rowspan = "2"|'''Mouse'''
|align = "center"|0.25
|align = "center"|0.56 ± 0.01
|-
|align = "center"|2.5
|align = "center"|0.48 ± 0.02
|-
|align = "center" rowspan = "2"|'''Rat'''
|align = "center"|0.25
|align = "center"|0.50 ± 0.02
|-
|align = "center"|2.5
|align = "center"|0.56 ± 0.03
|-
|align = "center" rowspan = "2"|'''Dog'''
|align = "center"|0.25
|align = "center"|0.52 ± 0.01
|-
|align = "center"|2.5
|align = "center"|0.52 ± 0.01
|-
|align = "center" rowspan = "2"|'''Monkey'''
|align = "center"|0.25
|align = "center"|0.69 ± 0.06
|-
|align = "center"|2.5
|align = "center"|0.62 ± 0.01
|-
|align = "center" rowspan = "2"|'''Human'''
|align = "center"|0.5
|align = "center"|0.54 ± 0.06
|-
|align = "center"|5
|align = "center"|0.60 ± 0.03
|}
{|border="2" cellspacing="0" cellpadding="4" width="62%"
|align = "center" bgcolor = "#9BBB59" colspan = "6"|'''A)Intrinsic clearance CLi, mL/min/g liver'''
|-
|align = "center"|
|align = "center" bgcolor = "#4F81BD"|'''Mouse'''
|align = "center" bgcolor = "#4F81BD"|'''Rat'''
|align = "center" bgcolor = "#4F81BD"|'''Dog'''
|align = "center" bgcolor = "#4F81BD"|'''Monkey'''
|align = "center" bgcolor = "#4F81BD"|'''Human'''
|-
|align = "center" bgcolor = "#4F81BD"|'''Microsomes'''
|align = "center"|0.7
|align = "center"|<nowiki><</nowiki>0.5
|align = "center"|<nowiki><</nowiki>0.5
|align = "center"|<nowiki><</nowiki>0.5
|align = "center"|<nowiki><</nowiki>0.5
|-
|align = "center" bgcolor = "#4F81BD"|'''Hepatocytes'''
|align = "center"|<nowiki><</nowiki>0.5
|align = "center"|3.7
|align = "center"|1.7
|align = "center"|<nowiki><</nowiki>0.5
|align = "center"|<nowiki><</nowiki>0.5
|-
|align = "center" bgcolor = "#9BBB59" colspan = "6"|'''B)CYP450 Inhibition IC50 µM'''
|-
|align = "center"|
|align = "center"|3A4
|align = "center"|1A2
|align = "center"|2D6
|align = "center"|2C9
|align = "center"|2C19
|-
|align = "center"|
|align = "center"|<nowiki>></nowiki>33
|align = "center"|<nowiki>></nowiki>33
|align = "center"|3.0 ± 1.8
|align = "center"|<nowiki>></nowiki>33
|align = "center"|<nowiki>></nowiki>33
|}