Pregabalin : Pharmacology

Pharmacokinetics

• After oral ingestion, Pregabalin is rapidly absorbed (Tmax 1.3 hr)
• Bioavailability is >90% and independent of dose
• Pregabalin is NOT protein bound
• Vd is 0.4 L/kg
• Serum pregabalin concentrations are linearly related to dosage
• Pregabalin is NOT metabolized
• Pregabalin is primarily excreted unchanged in urine (98%) with a clearance similar to the GFR
• Patients with impaired renal function show a reduced drug clearance and require a reduction in dosage
• The t1/2 elimination half life in serum is 4.6-6.8 hr

Recommended dose adjustments based on varying degrees of renal impairment

CrCl (mL/min)	Gabapentin	Pregabalin
59-30	700 mg BD	150 mg BD 100 mg TDS
29-15	700 mg OD	75 mg BD 50 mg TDS
<15	300 mg OD	75 mg OD
Hemodialysis supplemental doses post dialysis	100-300 mg	75-150 mg

Rowland Tozer Method

Q = 1 – [Fe * (1-KF)]

Q = drug dose adjustment factor

Fe = drug fraction excreted unchanged in urine

KF = ratio of patient’s CrCl to normal 120 ml/min

If CrCl = 60 ml/min, Fe = 0.98, KF = 0.5, Q = 0.51

i.e., Administer 50% dose at the normal dosing interval, or administer the normal dose at twice the dosing interval.

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Therapeutic Drug Monitoring

The role of TDM Therapeutic Drug Monitoring for Pregabalin has not yet been established and a reference range for the drug has yet to be identified.

There are 2 published methods for the determination of serum pregabalin.

1. HPLC with fluorescence detection
2. HPLC analysis by UV detection

Therapeutic and toxic ranges are not well defined.

Therapeutic concentrations are reported to be from 2 to 5 mcg/ml, while toxicity may occur at concentrations above 10 mcg/ml.

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Effects of other drugs on Pregabalin concentrations

Pharmacokinetic interactions with concurrently administered drugs are not expected because Pregabalin is neither bound to serum proteins not metabolized.

A study suggested that enzyme inducers AEDs (e.g., carbamazepine) can moderately decrease pregabalin serum concentration by +/- 20-30%.