Estimation of pharmacokinetic parameters of lithium from saliva and urine

Groth, Ulrich; Prellwitz, W.; Jähnchen, E.

doi:10.1002/cpt1974163part1490

Cited by 83 publications

(29 citation statements)

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“…The observations reported here show the consistency of elimination half-life, whether by measurement of red blood cells, plasma, or urine, con firming previous work that compared saliva, plasma, and urine [17],…”

Section: Discussionsupporting

confidence: 57%

“…The T./jE was found to be symmetrical around 12-13 h in serum. Groth et al [17] in a study of 3 healthy male subjects compared pharmacokinetic parameters in plasma, saliva, and urine after a single lithium dose of 10.8 or 40.6 mEq in lithium carbonate at 8 a.m. The T./2E was similar in the three fluids, varying from 14.2 to 24.1 h in plasma, from 12.7 to 26.3 h in saliva, and from 11.4 to 26.6 h in urine.…”

mentioning

confidence: 99%

“…There have been five further more recent studies that specifically focused on lithium elimination half-life (T,/AE) following acute dosage [1,2,17,29,30]. Amdisen [2] studied elimination in 177 patients and 49 volun teers following a dose at 6 p.m. of 16 or 24 mmol with follow-up blood drawing the next day at 8 a.m. and 3-4 p.m., respectively.…”

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confidence: 99%

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Lithium Pharmacokinetics, Duration of Therapy, and the Adenylate Cyclase System

Goodnick¹,

Fieve²,

Meltzer³

et al. 1982

Int Pharmacopsychiatry

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The elimination half-life of lithium carbonate in red blood cells, plasma, and urine was measured in 30 patients hospitalized for primary affective disorders. The duration of lithium treatment at the time of sampling was found to have a direct effect on lengthening time-course. Those on their initial course of litium had the lowest half-lives (in days): 1.12 (urine), 1.28 (plasma), and 1.22 (red blood cells); those with less than 1 year of lithium had intermediate values: 1.85, 1.65, and 1.75, and those with more than 1 year of continuous lithium administration had the highest mean half-lives: 2.40, 2.43, and 2.24. The significance of these results for urine (p < 0.01) and plasma (p < 0.05) indicates further evidence that lithium may stimulate the production of an endogenous regulator of lithium efflux. 8 of these patients had lumbar punctures before lithium administration: those with previous treatment with lithium had higher mean cyclic adenosine monophosphate levels than those taking it for the first time. These results are discussed in the context of the possible mechanisms of lithium action.

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Section: Discussionsupporting

confidence: 57%

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confidence: 99%

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Lithium Pharmacokinetics, Duration of Therapy, and the Adenylate Cyclase System

Goodnick¹,

Fieve²,

Meltzer³

et al. 1982

Int Pharmacopsychiatry

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“…Another hypothesis is that fluconazole is excreted in saliva not only by a process of passive diffusion but also by an active transport mechanism. Active transport has been described for several drugs including lithium (12), penicillin (3), and phenytoin (1). However, the fact that the S/P ratio was similar in irradiated patients does not support the active transport of fluconazole, since irradiation usually decreases or abolishes such mechanisms.…”

Section: Resultsmentioning

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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“…A previous study showed that serum lithium levels decline monoexponentially after being distributed in the fluid compartment, with a half-life of approximately 20 h [19]. Therefore, over the 2 1-hour urine collection periods, the deviation of serum lithium concentration from the linear regression line is small, and a single serum sample obtained at the midpoint of the urine collection is adequate for calculation of the renal clearance of lithium.…”

Section: Methodsmentioning

confidence: 97%

Decreased Lithium Clearance in Patients with Hyperthyroidism

Owada¹,

Tomita²,

Ujiie³

et al. 1993

Nephron

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Lithium clearance was studied to investigate proximal tubular function in patients with hyperthyroidism (n = 10) and control subjects (n = 7). Patients with hyperthyroidism showed significantly reduced fractional excretion of lithium (FELi) compared with control subjects (15.0 ± 1.5%, n = 10, vs. 23.7 ± 0.6%, n = 7, means ± SE, p < 0.001). The reduced FELi of the hyperthyroid state was reversed toward control values with treatment by antithyroid drugs (12.6 ± 2.6 toward 26.8 ± 2.5% for 5 patients, means ± SE). Tubular reabsorption of phosphate (TRP) was significantly increased in hyperthyroid patients compared with control subjects (96.1 ± 0.7 vs. 87.5 ± 0.7%, p < 0.001), and it returned to control values after the treatment. Our data demonstrate that lithium clearance is decreased and TRP is increased in patients with hyperthyroidism, which suggests that proximal tubular reabsorption of sodium and TRP is increased in hyperthyroidism.

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Estimation of pharmacokinetic parameters of lithium from saliva and urine

Cited by 83 publications

References 0 publications

Lithium Pharmacokinetics, Duration of Therapy, and the Adenylate Cyclase System

Lithium Pharmacokinetics, Duration of Therapy, and the Adenylate Cyclase System

Influence of local radiotherapy on penetration of fluconazole into human saliva

Decreased Lithium Clearance in Patients with Hyperthyroidism

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