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.
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.
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%.
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). Hard worker, Reliable, Team player, Family man.