Saliva secretion of chloroquine in man

Ogubona, F A; Lawal, Adebayo; Onyeji, Cyprian O.

doi:10.1111/j.2042-7158.1986.tb04632.x

Cited by 14 publications

(8 citation statements)

References 9 publications

(1 reference statement)

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“…In bile-duct-cannulated rats, Barrow ( 1974) showed that less than 5 % of administered chloroquine is excreted in bile and more than 40% in urine during the first 48 hours. Chloroquine has also been shown to be excreted in human saliva, representing about 1-2% of the administered dose (Ogunbona et al, 1987a). After a single 600 mg oral dose of chloroquine, about 0.7% was excreted in human milk.…”

Section: Blood Concentration-time Profiles and Elimination Routesmentioning

confidence: 99%

Antimalarial 4‐aminoquinolines: mode of action and pharmacokinetics

Pussard

Verdier

1994

Fundamemntal Clinical Pharma

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In the last ten years, the widespread increase in Plasmodium falciparum resistance to chloroquine has prompted research into antimalarial 4-aminoquinolines, empirically used up to now. The mechanism of action of 4-aminoquinolines is characterized by the concentration of the drug in the digestive vacuole of the intraerythrocytic parasite. Various hypotheses have been advanced to explain the specificity of action on the parasite; the most recent one is the inhibition of the haem polymerase of the parasite, leading to the accumulation of soluble haem toxic for the parasite. Chloroquine-resistant parasites accumulate the drug to a lesser extent than do sensitive parasites. Recent findings have shown that chloroquine resistance can be reversed by various tricyclic drugs, which are able to restore the effective concentrations of chloroquine in the infected erythrocyte, but intrinsic mechanisms of action of these reversing agents are unknown. Four-aminoquinolines are extensively distributed in tissues and characterized by a long elimination half-life. Despite similarities in their chemical structures, these drugs show differences in their biotransformation and routes of elimination: chloroquine is partly metabolized into a monodesethylderivative and eliminated mainly by the kidney. In contrast, amodiaquine is a prodrug and amopyroquine is poorly metabolized; both drugs are excreted mainly in the bile. The understanding of the pharmacokinetics of 4-aminoquinolines has led to an improvement in empirically defined therapeutic regimens. Finally, the emergence of severe adverse-effects after prolonged prophylaxis with amodiaquine and the lack of cross resistance of Plasmodium falciparum between chloroquine and amopyroquine, have led to a proposal for the use of intramuscular amopyroquine as an alternative for the treatment of chloroquine-resistant malaria.

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Section: Blood Concentration-time Profiles and Elimination Routesmentioning

confidence: 99%

Antimalarial 4‐aminoquinolines: mode of action and pharmacokinetics

Pussard

Verdier

1994

Fundamemntal Clinical Pharma

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“…Among these events, irradiation of the salivary glands at a dose greater than 45 Gy results in stomatitis, opportunistic infections (especially candidiasis), increased viscosity of saliva, and qualitative and quantitative modifications of its composition (14,20,22). These modifications are able to decrease penetration of drugs into the salivary gland (13,18). Although there is no clear relation between fluconazole levels in saliva and clinical outcome, very low levels in saliva or absence of saliva caused by irradiation would be a priori detrimental to efficacy.…”

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confidence: 99%

Influence of local radiotherapy on penetration of fluconazole into human saliva

Oliary

Tod

Louchahi

et al. 1993

Antimicrob Agents Chemother

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The pharmacokinetics of fluconazole (50 mg, single oral dose) in saliva and plasma were determined for five healthy subjects and five patients who underwent radiotherapy (dose, >45 Gy over a 6-week period) in the salivary gland area and suffered from oropharyngeal candidiasis. Saliva was collected after electrical stimulation. Fluconazole was measured by liquid chromatography. From healthy volunteers and patients, saliva and plasma were sampled from 0 to 24 h. Although fluconazole penetration kinetics were significantly slowed down in irradiated patients, saliva concentrations of fluconazole were higher than those in the plasma, except at 1 h. In the postdistribution phase, the saliva/plasma concentration ratio was in the range of 1.2 to 1.4, and there was no significant difference between healthy subjects and patients. The saliva concentration of fluconazole was over 1 mg/liter throughout the entire interval 2 to 24 h after drug intake. From these results, the clinical efficacy of fluconazole for oropharyngeal candidiasis is not expected to be less than that in subjects with normal salivary glands, provided that salivary secretion remains.Fluconazole is a broad-spectrum antifungal agent approved in several countries for the treatment of some superficial and deep mycoses. Comparative trials have shown fluconazole to be equal or superior to ketoconazole in the treatment of oropharyngeal candidiasis in patients with AIDS (7) or cancer (17). Fluconazole exhibits a high penetration into body tissues as demonstrated recently by positron emission tomography (9). The volume of distribution of fluconazole approximates that of total body water, the drug exhibits a low level of protein binding (12%) to plasma proteins, and concentrations in saliva, sputum, and vaginal and blister fluid equal those measured in plasma (4). Fluconazole also penetrates into the central nervous system, with levels in the cerebrospinal fluid between 50 and 90% of corresponding levels in plasma, even in the absence of meningitis (11). However, physiological or pathological events can affect tissue penetration and thus possibly clinical outcome. Among these events, irradiation of the salivary glands at a dose greater than 45 Gy results in stomatitis, opportunistic infections (especially candidiasis), increased viscosity of saliva, and qualitative and quantitative modifications of its composition (14,20,22). These modifications are able to decrease penetration of drugs into the salivary gland (13, 18). Although there is no clear relation between fluconazole levels in saliva and clinical outcome, very low levels in saliva or absence of saliva caused by irradiation would be a priori detrimental to efficacy. Indeed, the only clinical failure in the study by Dupont and Drouhet (8) was in an irradiated patient who had no salivary secretion. Thus, the pharmacokinetic parameters describing fluconazole assimilation into saliva were determined for a population of patients who underwent radiotherapy in the salivary gland area.* Corresponding author. MATERIA...

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“…4), which predicts the presence of a compound desethylchloroquine. Ogubona et al [18] reported that desethylchloroquine drug and its metabolites are secreted in the human saliva. The research findings of Dorn et al [19] proves that desethylchloroquine possess antiplasmodic activity [19].…”

Section: Resultsmentioning

confidence: 99%