Lithium pharmacokinetics

Excessive use of alcohol can interfere with adherence to lithium therapy. Alcohol does not itself appear to alter lithium pharmacokinetics (574). 

In a placebo-controlled, parallel-design, double-blind study in 24 male volunteers, amisulpride 100 mg bd for 7 days did not alter lithium pharmacokinetics (623). 

There were no changes in lithium pharmacokinetics when risperidone was substituted open-label for another neuroleptic drug in 13 patients (634). On the other hand, an 81-year-old man had an acute dystonic reaction 4 days after lithium was added to a regimen of risperidone, valproic acid, and benzatropine (635). 

Frye MA, Kimbrell TA, Dunn RT, Piscitelli S, Grothe D, Vanderham E, Cora-Locatelli G, Post RM, Ketter TA. Gabapentin does not alter single-dose lithium pharmacokinetics. J Chn Psychopharmacol 1998 1 8(6) 461 —4. 

The effect of lamotrigine on steady-state lithium pharmacokinetics has been studied in 20 healthy adult men (75). Lamotrigine did not significantly change the pharmacokinetics of lithium. 

As might be expected, the presence of food in the gastrointestinal tract has been shown to affect lithium absorption and a diurnal variation in renal lithium clearance has been reported 183, 184). In our experiments, diurnal and other factors appeared to influence lithium pharmacokinetics to a greater degree than did formulation differences 182). We conclude that the practice of administering an early evening dose after a meal may delay the lithium peak sufficiently to reduce the possible discomfort of any transient side effects and may improve patient compliance. This is more important than the choice of preparation to be given. 

Chang SS, Pandey GN, Yang YY, et al Lithium pharmacokinetics interracial comparison. Paper presented at the annual meeting of the American Psychiatric Association, Dallas, TX, May 19-24,1985... 

Lithium metabolism and transport cannot be studied directly, because the lack of useful radioisotopes has limited the metabolic information available. Lithium has five isotopes, three of which have extremely short half lives (0.8,0.2, 10 s). Lithium occurs naturally as a mixture of the two stable isotopes Li (95.58%) and Li (7.42%), which may be determined using Atomic Absorption Spectroscopy, Nuclear Magnetic Resonance Spectroscopy, or Neutron Activation analysis. Under normal circumstances it is impossible to identify isotopes by using AAS, because the spectral resolution of the spectrometer is inadequate. We have previously reported the use of ISAAS in the determination of lithium pharmacokinetics. Briefly, the shift in the spectrum from Li to Li is 0.015 nm which is identical to the separation of the two lines of the spectrum. Thus, the spectrum of natural lithium is a triplet. By measuring the light absorbed from hollow cathode lamps of each lithium isotope, a series of calibration curves is constructed, and the proportion of each isotope in the sample is determined by solution of the appropriate exponential equation. By using a dual-channel atomic absorption spectrometer, the two isotopes may be determined simultaneously. - ... 

Lithium pharmacokinetics may be influenced by a number of factors, including age. Elderly patients require lower doses of lithium to achieve serum concentrations similar to those observed in younger adults as a result of reduced volume of distribution and... 

In a study in 24 healthy subjects, lithium carbonate 500 mg twice daily was given for 7 days to obtain stable lithium serum levels, and then amisulpride 100 mg twice daily or placebo was added for a further 7 days. Amisulpride appeared to have no effect on lithium pharmacokinetics. In a pharmacokinetic analysis of amisulpride levels in patients with schizophrenia or schizoaffective disorder, dose-corrected amisulpride plasma levels were 1.8-fold higher in 3 patients taking lithium than in 13 patients taking amisulpride alone. Further study is needed to confirm this finding and establish its clinical significance. 

Potkin SG, TI Tum PT, Bera R, Caneai D, Alva G, Kalali AH, Yeh C. Open-label study of die effect of combination queti ine/lilhium tiier y on lithium pharmacokinetics and tolerability. Clin Ther (2002) 24,1809-23. 

Extrapyramidal adverse effects have been seen in a patient taking risperidone and lithium. No changes in lithium pharmacokinetics are expected. 

Beijnen JH, Bais EK4 ten Bokkel Huinink Lithium pharmacokinetics during cisplatin-based chemotherapy acase report. Cancer Chemother Pharmacol ( 99A) 33,523-6. 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

TABLE 36-5. Pharmacokinetics and Therapeutic Serum Concentrations of Lithium and Anticonvulsants Used in the Treatment of Bipolar Disorder... 

In contrast to the limited value of pharmacokinetics to the use of antidepressants, knowledge of the kinetics of lithium has been important in defining the therapeutic and toxic range in unipolar or bipolar manic patients. Prediction of the dose required by the individual patient by giving a single dose of the drug and measuring the erythrocyte/plasma lithium... 

Pharmacology Lithium alters sodium transport in nerve and muscle cells, and effects a shift toward intraneuronal catecholamine metabolism. The specific mechanism in mania is unknown, but it affects neurotransmitters associated with affective disorders. Its antimanic effects may be the result of increases in norepinephrine reuptake and increased serotonin receptor sensitivity. Pharmacokinetics ... 

Sproule BA, Hardy BG, Shulman Kl. Differential pharmacokinetics of lithium in elderly patients. Drugs Aging 2000 16 165-177. 

FIGURE 4.4 A Lithium plasma concentration time profile based on a population pharmacokinetics model (Taright et al., 1994). Closed circles are the actual measured lithium concentrations broken lines represent the therapeutic range (0.6-1.2 mmol/L). B Individualized lithium plasma concentration time profile based on the population model with feedback of measured concentrations (Bayesian recalculation). Closed circles are the measured lithium concentrations. The second part of the curve is the predicted lithium concentration profile after increasing the dose to 1000 mg lithium carbonate twice daily, based on a target of 0.6-1.2 mmol/L (broken lines). 

In this chapter we review the mechanisms of action, pharmacokinetics, side effects, and uses of lithium and the anticonvulsants as they apply to child psychiatric clinical practice. 

Eaton WW, Kessler RC, Wittchen ElU, et al Panic disorder and panic in the United States. Am J Psychiatry 151 413-420, 1994 Ebadi MS, Simmons VJ, Hendrickson MJ, et al Pharmacokinetics of lithium and its regional distribution in rat brain. Eur J Pharmacol 27 324-329, 1974 Ebert D, Feistel H, Kaschka W, et al Single photon emission computerised tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation—preliminary results. Biol Psychiatry 35 880-885, 1994... 

Hokin-Neaverson M, Burckhardt WA, Jefferson JW Increased erythrocyte Na" pump and Na-K-ATPase activity during lithium therapy. Research Communications in Chemical Pathology and Pharmacology 14 117-126, 1976 Holazo AA, Winkler MB, Patel IH Effects of age, gender and oral contraceptives on intramuscular midazolam pharmacokinetics. J Clin Pharmacol 28 1040-1045, 1988... 

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