Cycloserine dosing

Because they are hepatically cleared, isoniazid and rifampin do not require dose modification in renal failure.31,36,39 Pyrazinamide and ethambutol typically are reduced to three times weekly to avoid accumulation of the parent drug (ethambutol) or metabolites (pyrazinamide).28,31 Renally cleared TB drugs include the aminoglycosides (e.g., amikacin, kanamycin, and streptomycin), capreomycin, ethambutol, cycloserine, and lev-ofloxacin.28,31,33,39 Dosing intervals need to be extended for... 

Cycloserine Adults8 10-15 mg/kg per day, usually 500-750 mg/day in two doses Children 10-15 mg/kg per day Central nervous system effects Monthly assessments of neuropsychiatric status Serum concentration may be necessary until appropriate dose is established... 

Cycloserine Yes 250 mg once daily, or 500 mg/dose three times per week1... 

D-Cycloserine is a central partial agonist of NMDA receptors in place of P-glycine, which in low doses has shown an antagonism of cognitive deterioration induced by scopolamine. Confusion, disorientation, and memory loss have been observed at high doses. D-Cycloserine can provide a symptomatic treatment of AD at low dosage (Bowen et al. 1992 B. L. Schwartz et al. 1996). 

Cycloserine causes serious dose-related central nervous system toxicity with headaches, tremors, acute psychosis, and convulsions. If oral dosages are maintained below 0.75 g/d, such effects can usually be avoided. 

Cycloserine is an inhibitor of cell wall synthesis and is discussed in Chapter 43. Concentrations of 15-20 mcg/mL inhibit many strains of M tuberculosis. The dosage of cycloserine in tuberculosis is 0.5-1 g/d in two divided doses. Cycloserine is cleared renally, and the dose should be reduced by half if creatinine clearance is less than 50 mL/min. 

It should be noted that, although this is the dose recommended generally, most clinicians with experience using cycloserine indicate that it is unusual for patients to be able to tolerate this amount. Serum concentration measurements are often useful in determining the optimal dose for a given patient,... 

Cycloserine Yes 250 rng once daily, or 500 m dose three times pet weelf... 

RenaUy cleared TB drugs include the aminoglycosides (amikacin, kanamycin, and streptomycin), capreomycin, ethambutol, cycloserine, and levofloxacin. " " Dosing intervals need to... 

Ethionamide and its sulfoxide metabolite are cleared hepati-cally, so dosing is unchanged. °p-Aminosalicylic acid is converted largely to metabolites prior to renal elimination these metabolites may accumulate in renal failure. For patients on hemodialysis, the usual 12-hour dosing interval for p-aminosalicylic acid granules seems to be safe. Dialysis will remove the metabolites. Serum concentration monitoring must be performed for cycloserine to avoid dose-related toxicities in renal failure patients... 

Data are not available for dosing the TB drugs in patients with morbid obesity." Relatively hydrophilic drugs (isoniazid, pyrazinamide, the aminoglycosides, capreomycin, ethambutol, p-aminosalicylic acid, and cycloserine) can be dosed initially based on ideal body weight... 

When given orally, 70—90% of cycloserine is rapidly absorbed. Cycloserine is distributed throughout body fluids and tissues. CSF concentrations are comparable to those in plasma. About 50% of a parenteral dose of cycloserine is excreted unchanged in the urine in the first 12 hours a total of 65% is recoverable in the active form over a period of 72 hours. Very little of the antibiotic is metabolized. The drug may reach toxic concentrations in patients with renal insufficiency it is removed from the circulation by hemodialysis. 

Cycloserine is used only when retreatment is necessary or microorganisms are resistant to other drugs. It must be given together with other effective agents. The usual dose for adults is 250-500 mg twice daily. 

Side effects typically effect the CNS, appearing within 2 weeks of therapy and disappearing after drug withdrawal. They include somnolence, headache, tremor, dysarthria, vertigo, confusion, nervousness, irritability, psychotic states, paranoid reactions, catatonic reactions, twitching, ankle clonus, hyperreflexia, visual disturbances, paresis, and seizures. Large doses or concomitant ingestion of alcohol increases the risk of seizures. Cycloserine is contraindicated in individuals with a history of epilepsy and should be used with caution in individuals with a history of depression. 

A study in 12 healthy subjects found that the bioavailability of a single 500-mg dose of cycloserine was not affected by 15 mL oiMylanta (aluminium hydroxide 400 mg, magnesium hydroxide 400 mg, simeticone 40 mg per 5 mL). Mylanta was given 9 hours before the eyeloserine, at the same time as the cycloserine, immediately after meals, and at bedtime on the dosing day and following day. ... 

Fig. 2. SAM and SAH content in liver tissue of mice and rats treated with D-cycloserine and cis-APD. D-Cycloserine was injected i.p. into mice (A) in dose a 4.0 gm/kg of body weight. cis-APD was injected i.p. into rats (B) three times with intervals of 2 hr, each time in a dose of 1.0 gm/kg of body weight. At the specifed time intervals after the injections of D-cycloserine or first injection of cis-APD the animals were killed for assay of SAM and SAH content and activity of serine transhydroxymethylase. Symbols (—Q—),SAM ...

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