Therapeutic drug monitoring

Cyclosporine

Cyclosporine is indicated for the treatment of atopic dermatitis in dogs and cats and is also used in the management of certain immune-mediated diseases. Serum concentrations do not correlate well with the clinical response and therapeutic drug monitoring is not usually indicated.

Measurement of the drug concentration in a trough sample at 12 or 24 hours post medication may be useful if the clinical signs are refractory, to determine whether this is due to inadequate dosing.

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Carbimazole and thiamazole (methimazole)

It is recommended that total T4 (TT4), haematology and biochemistry are assessed 2-3 weeks after starting therapy or any dose alteration until the patient is euthyroid, 3 months later and then every 6 months. The timing of the sample in relation to the administration of the medication is not critical but regular dosing is essential since a return to hyperthyroidism is noted within 24-48 hours of discontinuation of therapy. The aim should be to maintain T4 within the lower half of themreference interval to maximise the clinical response and avoid adverse effects on renal function.

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Phenobarbitone

Phenobarbitone should be given for about 2-3 weeks to allow for serum levels to stabilise before checking therapeutic concentrations. Once a steady serum state is achieved, a sample for routine monitoring may be collected at any time after dosing, although subsequent samples should ideally be taken at the same time for an individual patient. However, if toxicity is suspected a peak level (4-6 hours post-pill) should be measured and if clinical response is poor a trough sample may be useful. Serum concentrations should be evaluated in conjunction with the clinical response.

Hepatic function should be assessed prior to therapy and monitored every 6-12 months in dogs, hepatotoxicity is not reported in cats. Haematology may also be monitored, due to the potential for cytopaenias to occur as an idiosyncratic reaction.

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Potassium bromide

Potassium bromide has a long half life (24 days) and in the dog serum concentrations may take 3-4 months to stabilise. The drug concentration can be assessed at any time after dosing.

Collection of interim samples every 4 weeks for the first 3 months of therapy is recommended. At 4 weeks, concentrations will be approximately half that achieved at steady state. Loading protocols are available for more rapid control of seizures and in these cases serum concentration should be measured at the end of loading. Renal elimination of bromide is directly proportional to the chloride intake and it is important to ensure a stable dietary chloride intake to avoid bromide fluctuations. It is recommended that KBr concentrations are checked 6-12 weeks after a significant change in diet or a change in the dose of drug, then at 6-12 month intervals once clinically stable.

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Digoxin

Digoxin should be given for 5-7 days to allow serum concentrations to stabilise prior to monitoring. A variety of testing protocols have been suggested but most sources recommend sampling around 8 hours after medication.

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Thyroid supplementation

Assessing therapy on the day of sampling. Samples can be taken after 2-4 weeks of therapy. Due to individual variation in the half life of thyroxine, collection of peak (4 hours post medication) and trough samples provides the most reliable information. However, where this approach is not practicable, it is possible to collect one sample, at least 2 hours after administration of medication, and to extrapolate the expected T4 concentrations (based on the reported drug half-life) for the remainder of the day. To provide a patient with a therapeutic graph, the time of sampling in relation to the last medication (at least two hours) and frequency of dosing is required.

A trough sample may be more helpful to assess once daily therapy.

Ideally, the normal daily feeding and medication regime should be maintained on the day of testing. Administration of thyroxine in relation to feeding (timing, food type and amount) in hypothyroid dogs should be consistent to avoid significant variation in absorption.

Assessing adequacy of supplementation over the last few days. The TSH concentration gives an indication of the adequacy of therapy over the previous few days. This can help identify inconsistencies in dosing/absorption and also prevent an inappropriate management decision being made based on a non-representative single TT4 result.

Trilostane

The datasheet recommendation is that trilostane should be monitored by performing an ACTH stimulation test (basal and 1 hour post ACTH) at 4-6 hours after dosing. Monitoring of biochemistry including electrolyte concentrations is also recommended.

However, more recent work suggests that measurement of cortisol immediately pre-trilostane and 3 hours after dosing in combination with a clinical scoring system (available from the drug manufacturer) correlates better with the clinical response. This may also be helpful given the supply issues regarding Synacthen.

Monitoring should be performed after 10 days, 4 weeks and 12 weeks of therapy (and after any dosage change) and then every 3 months.

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Imepitoin

Therapeutic monitoring is not indicated since the rapid plasma half life makes it unlikely that a steady serum state is ever achieved. However, imepitoin is rapidly absorbed across the blood brain barrier and therapeutic concentrations persist within the CNS over a much longer period of

time.

Gabapentin

Monitoring serum concentrations does not appear to be useful in dogs (or humans). However, a proposed canine therapeutic range is 4-16mg/l or 23.36-93.44umol/l. We are able to derive a therapeutic monitoring sheet from figures quoted in Vet Clinics of North America: Small Animal Practice 2006 ; Vol 36, Issue 5 Current topics in clinical pharmacology and therapeutics. Anticonvulsant therapy in dogs by Curtis E Dewey, p 1107-1127 if required.

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Levetiracetam

A therapeutic range has not been well defined for the dog or cat and a steady serum state is not achieved, however, the pharmacodynamic effect is believed to outlive the known half life. Monitoring serum concentrations is only likely to be helpful in establishing the pharmacokinetics for the individual patient, due to the variable drug metabolism.

Authors & References

NationWide Laboratories