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.
- HPLC with fluorescence detection
- 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%.
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MBChB (O’Porto Univ.), Dip HIV Man (CMSA), DTM&H (Wits), DipPEC (CMSA), Dip Internal Medicine (CMSA), M. Med. Clinical Pharm [Cum Laude] (Univ. Pretoria), FCP (CMSA)