Atovaquone antimalarial

Atenolol - beta blocker hypertension, angina, arrhythmia Atomoxetine - CNS stimulant treatment of ADHD Atorvastatin - statin lipid lowering drug Atovaquone - antimalarial... 

Atovaquone, a hydroxynaphthoquinone (Figure 52-2), was initially developed as an antimalarial agent, and as a component of Malarone is recommended for treatment and prevention of malaria. Atovaquone has also been approved by the FDA for the treatment of mild to moderate P jiroveci pneumonia. 

Toxoplasmosis Lymph nodes many organs and tissues Pyrimethamine-sulfadiazine [see antimalarial drugs] other antibacterials [clindamycin] Trimethoprim-sulfamethoxazole another agent [azithromycin, clarithromycin, atovaquone, or dapsone]... 

Clinical Use. Atovaquone (Mepron) is used primarily to treat the protozoon that causes toxoplasmosis and the fungus that causes pneumocystis pneumonia in immunocompromised patients.6 This drug is not typically the primary treatment for pneumocystis, but is often reserved for patients who cannot tolerate more traditional treatments using sulfamethoxazole and trimethoprim (see Chapter 34) or pentamidine (see later). Atovaquone can also be used to prevent and treat resistant cases of malaria, and the antimalarial effects of this drug seem especially useful when combined with proguanil.48... 

METOCLOPRAMIDE ANTIMALARIALS -ATOVAQUONE 1 atovaquone levels Uncertain Avoid consider an alternative antiemetic... 

RIFAMYCINS ANTIMALARIALS -ATOVAQUONE Both rifampicin and rifabutin L atovaquone levels, although the effect is greater with rifampicin (1AUC 50% cf. with 34% rifabutin) Uncertain because atovaquone is predominantly excreted unchanged via the gastrointestinal route Avoid co-administration with rifampicin. Take care with rifabutin and watch for poor response to atovaquone... 

ATOVAQUONE H2 RECEPTOR BLOCKERS - CIMETIDINE t efficacy and adverse effects of antimalarials Inhibition of metabolism, some definitely via CYP3A4 Avoid co-administration... 

Proguanil is one of the antimalarial drugs most widely used for prophylactic purposes, usually in combination with chloroquine or atovaquone in malaria prophylaxis, and with atovaquone in malaria treatment (SEDA-21, 297). A biguanide, it is rapidly absorbed in standard doses and mainly excreted by the kidneys. Its antimalarial effect is due to its metabolite cycloguanU. However, its metabolism varies individually, and this is reflected in a variable degree of efficacy (SEDA-17, 328). 

In addition to metabolism, the liver is also able to secrete unchanged drug into the bile, sometimes against a high concentration gradient. This is also a form of hepatic clearance. An example of a drug that is almost exclusively eliminated by biliary secretion is the antimalarial drug atovaquone. 

Looareesuwan, S., Viravan, C., Webster, H. K., Kyle, D. E., Hutchinson, D. B., and Canfield, C. J. (1996). Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am. J. Trop. Med. Hyg. 54, 62-66. 

Atovaquone is an antimalarial preparation. It inhibits mitochondrial electron transport in parasites, causing inhibition of nucleic acid synthesis. Proguanil exerts its effect by means of the metabolite cycloguanil, which inhibits dihydrofolate reductase in the malarial parasite, disrupting deox-ythymidylate synthesis. It is indicated in prophylaxis of P. falciparum in patients with severe renal impairment (Ccr less than 30 mL/min) hypersensitivity to any component of the product. 

FIGURE 39-2 Spectrum of clinically useful activity for antimalarial drugs. For atovaquone and proguanil, reliable activity against the primary liver stage has been shown for P. falciparum only for the class 1 agents, activity against... 

The mechanism of the antimalarial activity of proguanil or chlorproguanil is unknown. Proguanil as the biguanide accentuates the mitochondrial membrane-potential-collapsing action of ato-vaquone against P. falciparum but displays no such activity by itself (see Atovaquone, above). 

In contrast to cycloguanil, resistance to the intrinsic antimalarial activity of proguanil itself, either alone or in combination with atovaquone, has yet to be documented. 

TETRACYCLINE ANTIMALARIALS- ATOVAQUONE i atovaquone levels (40%) Uncertain Not clinically significant combination therapy has been used effectively... 

Atovaquone, a chemical with structural similarity to the ubiquinone metabolites, was initially synthesized and investigated as an antimalarial, a use for which it has recently gained acceptance when used in combination therapy with other antimalarial agents. Today, its usefulness is primarily directed toward the treatment of PCP. 

Srivastava IK, Vaiefya AB. A mechanism for the S3fnergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother (1999) 43,1334-9. 

An in vitro study found that doxycycline potentiated the antimalarial activity of atovaquone, but there appears to be no information on the effect of doxycycline on the absorption of atovaquone. A study looking at the population pharmacokinetics of atovaquone in 24 Thai patients found that neither the oral clearance nor the volume of distribution of atovaquone were significantly affected by the concurrent use of tetracycline. ... 

Beitani et al. [100] also showed that SkD was inactive against heme biomineralization process and did not affect permeability pathways induced by a parasite in the host erythrocyte membrane. They also showed that SkD enhanced the activity of atovaquone on Plasmodium mitochondrial membrane potential, while it had an additive effect when combined with other commercial antimalarials. 

Antimalarial drugs There were lower concentrations of atovaquone -I- proguanil in HIV-infected individuals taking efavirenz. The authors compared the pharmacokinetics of atovaquone -I- proguanil between healthy volunteers and HIV-infected patients taking efavirenz and found that the geometric mean ratio AUCo x for... 

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