Levodopa
Levodopa. Dopamine prodrug — crosses the BBB via LAT1 (dopamine does not). Decarboxylated by AADC to dopamine both centrally and peripherally.… Oral half-life 1.5 h.
Dopamine prodrug — crosses the BBB via LAT1 (dopamine does not). Decarboxylated by AADC to dopamine both centrally and peripherally. Carbidopa (peripheral AADC inhibitor) is co-administered to prevent peripheral dopamine formation (nausea, hypotension) and preserve more L-DOPA for CNS conversion.
PK: its cited paper is an INTRAVENOUS-INFUSION study containing NO NUMERIC PHARMACOKINETIC VALUE AT ALL, only "50%" and "doubles" — zero-content and route mismatch together — and its second reference is a pyridoxine study with no levodopa kinetics. F 0.3 CAN ONLY DESCRIBE LEVODOPA GIVEN WITHOUT A DECARBOXYLASE INHIBITOR, which is the one situation that essentially never occurs clinically; that same paper states carbidopa DOUBLES oral bioavailability. F is therefore pinned to 1 and the volume stored as the published apparent 42.9 L from a fit that also supplies the absorption rate. NEITHER A FIXED RATE NOR A FIXED BIOAVAILABILITY IS DEFENSIBLE: absorption is through a SATURABLE transporter shared with dietary large neutral amino acids and competing with protein intake, exposure is dose-nonlinear, and the between-subject variability on the absorption rate is 122%. The effect-compartment value verifies and is kept, but it describes the SHORT-DURATION response only; the days-long long-duration response is not representable by it, and the same source notes carbidopa "did not change the duration of the clinical response".
Pharmacokinetics
- Oral — t½ 1.5 h · F 100% · ka 1.86 h⁻¹ · Vd 42.9 L
Related compounds
- Tyrosine — synergistic
- Dopamine — synergistic
- Vitamin B6 — caution
Sources: PMID:4073849, PMID:8112370, PMID:21080186