| Field | Value |
|---|---|
| Age | 50 years |
| Sex | Male |
| Diagnosis | Possible CBS/PSP (alpha-synuclein negative) |
| Current Medications | Levodopa, Rasagiline |
Levodopa (combined with carbidopa) is the cornerstone of dopaminergic therapy for parkinsonian syndromes. While primary metabolism occurs via COMT (Catechol-O-methyltransferase) in the periphery, genetic variants affecting response include:
| Gene | Polymorphism | Effect on Levodopa |
|---|---|---|
| COMT | Val158Met (rs4680) | Val/Val = faster metabolism, shorter "on" time; Met/Met = prolonged effect, more dyskinesias |
| SLC22A1 (OCT1) | Reduced function variants | May affect transport into CNS |
| SLC6A3 (DAT1) | 9/10 repeat variants | May affect dopamine reuptake and response duration |
Rasagiline is a selective, irreversible MAO-B inhibitor used as monotherapy or adjunct in Parkinson's disease. Key metabolic pathways:
| Enzyme | Role | Clinical Note |
|---|---|---|
| CYP1A2 | Minor pathway | Smoking inducers may reduce efficacy |
| CYP2C19 | Primary metabolism | Contributes to active metabolite formation |
| CYP3A4 | Secondary pathway | Strong inhibitors may increase exposure |
For this patient's specific medication regimen, the following genes should be prioritized:
| Gene | Why Test | Clinical Action |
|---|---|---|
| COMT (Val158Met) | Directly affects levodopa metabolism and response | Guide levodopa dosing frequency and COMT inhibitor use |
| CYP2C19 | Contributes to rasagiline metabolism | May need dose adjustment if PM or UM |
| Gene | Why Test | Clinical Action |
|---|---|---|
| CYP2D6 | Affects many concomitant medications | Important for future medication choices |
| CYP3A4 | Secondary pathway for rasagiline | Relevant for drug interactions |
| SLC22A1 | Affects levodopa transport | May influence dosing |
Recommended panels:
Based on genotype results, use the following guidance:
| Status | Rasagiline Recommendation |
|---|---|
| Poor Metabolizer (PM) | May have increased exposure; standard dose initially, monitor for side effects |
| Intermediate Metabolizer (IM) | Standard dosing |
| Normal Metabolizer (NM) | Standard dosing |
| Ultrarapid Metabolizer (UM) | May have reduced exposure; consider efficacy monitoring |
| Genotype | Levodopa Response | Recommendation |
|---|---|---|
| Val/Val | Faster metabolism, shorter "on" time | Consider: more frequent dosing (e.g., every 3-4 hours), earlier COMT inhibitor (entacapone) addition |
| Val/Met | Intermediate | Standard regimen, monitor |
| Met/Met | Slower metabolism, prolonged effect | Consider: lower doses if dyskinesias develop, monitor for wearing-off |
Given the patient's current regimen:
Levodopa/Carbidopa
Rasagiline
For Val/Val COMT patients:
For Met/Met COMT patients:
For CYP2C19 PM:
Avoid with rasagiline:
Monitor with:
| Interaction | Effect | Management |
|---|---|---|
| High-protein meals | Reduced absorption | Take 30-60 min before meals |
| Iron supplements | Reduced absorption | Separate by 2+ hours |
| Antipsychotics (dopamine blockers) | May reduce efficacy | Avoid or use lowest dose |
| Parameter | Frequency | Target |
|---|---|---|
| Motor function | Monthly | Stable "on" time, minimal dyskinesias |
| Blood pressure | Monthly | SBP >90, no symptomatic orthostasis |
| Mood/cognition | Every 3 months | Stable or improved |
| Adverse events | Ongoing | None or manageable |
This patient profile should be referenced when:
| Factor | Current Status | Action |
|---|---|---|
| Diagnosis | Possible CBS/PSP | Continue diagnostic workup |
| Levodopa | Standard regimen | Consider COMT genotyping to optimize |
| Rasagiline | 1 mg daily | Monitor efficacy; consider CYP2C19 testing if poor response |
| Testing | Not yet performed | Recommend COMT, CYP2C19 as priority |