|
| Medication | Blood site | Measured concentration
(mcg/mL) | Metabolism | Reference range | Drug-drug interactions | Comment |
|
| Diphenhydramine | Femoral/heart | 0.78/0.63
(toxic level) | 50% liver metabolism to diphenylmethane, which suggests a large first-pass effect | Antihistamine effects at levels >0.025 mcg/mL
Drowsiness at levels 0.03–0.04 mcg/mL
Mental impairment at levels >0.06 mcg/mL
Toxic: >0.1 mcg/mL
Therapeutic: not established | Metabolism/transport effects
inhibit CYP2D6
(moderate) and
CYP1A2, 2C9, and 2C19 (minor) | May increase fluoxetine level via inhibition of CYP2D6 |
|
| Fluoxetine | Femoral/heart | 1.8/2.3
(toxic level) | CYP450
(extensive P450 CYP2D6 inhibitor, demethylation)
Active metabolite:
norfluoxetine | Therapeutic: fluoxetine: 0.1–0.8 mcg/mL
Toxic: fluoxetine plus norfluoxetine: >2 mcg/mL | Metabolism/transport effects substrate of CYP1A2 (minor), 2B6 (minor), 2C9 (major), 2C19 (minor), 2D6 (major), 2E1 (minor), and 3A4 (minor)
It inhibits CYP1A2 (moderate), 2B6 (weak), 2C9 (weak), 2C19 (moderate), 2D6 (strong), and 3A4 (weak) | Avoid concomitant use with MAO inhibitors
Increased effect/toxicity of serotonin reuptake inhibitor/antagonist, carbamazepine, CNS depressants, CYP1A2 substrates, CYP2C19 substrates, CYP2D6 substrates, serotonin modulators |
|
| Norfluoxetine | Femoral/heart | 0.81/1.1 (toxic level) | Active metabolite of fluoxetine | Therapeutic:
norfluoxetine (active metabolite): 0.1–0.6 mcg/mL
Toxic: fluoxetine plus norfluoxetine: >2.0 mcg/mL | | Patient had combined fluoxetine + norfluoxetine 3.3 mcg/ml in heart blood, over the toxic limit 2.0 mcg/ml |
|
| Metoclopramide | Femoral/heart | 0.10/0.10 | Hepatic: minimal, via simple conjugation | N/A | Metabolism/Transport effects substrate of (minor) CYP1A2, 2D6;
it inhibits CYP2D6 (weak) | May increase fluoxetine level via inhibition of CYP2D6 |
|
| Mirtazapine | Femoral/heart | 0.19/0.11 | CYP450 extensively hepatic via CYP2D6, CYP1A2,
CYP2C9, and CYP3A4
Metabolites:
8-hydroxyl metabolite,
N-desmethyl, and N-oxide metabolites | N/A | Metabolism/transport effects substrate of CYP1A2 (major), 2C9 (minor), 2D6 (major), and 3A4 (major)
It inhibits CYP1A2 (weak), 3A4 (weak) | May increase levels/effects of CNS depressantsSerotonin modulators
The level/effects of mirtazapine may be increased by CYP1A2 inhibitors (strong), 2D6 inhibitors (moderate), CYP3A4 inhibitors (moderate) |
|
| Tramadol | Femoral/heart | 0.2/0.17 | Extensively hepatic via demethylation, glucuronidation, and sulfation
Pharmacologically active metabolite formed by CYP2D6 (M1; O-demethyl tramadol) | 0.1–0.3 mcg/mL
However, serum level monitoring is not required | Metabolism/transport effects substrate of CYP2D6 (major), 3A4 (major) | May increase levels/effects of CNS depressants; MAOI; SSRIs:
Serotonin modulators
The level/effects of tramadol may be increased by CYP2D6 inducers (moderate), 3A4 inhibitors (strong)
The levels/effects of tramadol may be decreased by CYP2D6 inhibitors
(moderate), 3A4 inducers (strong) |
|
| Nortramadol | Femoral/heart | 0.82/0.84 | Active metabolite of tramadol | 0.1–0.3 mcg/mL
However, serum level monitoring is not required | | |
|
| Lidocaine | Heart | <0.5 | CYP450
90% hepatic metabolism via CYP1A2
Active metabolites:
Monoethylglycinexylidide (MEGX)
Glycinexylidide (GX) | Therapeutic:
1.5–5 mcg/mL
Potentially toxic levels:
>6 mcg/mL
Toxic:
>9 mcg/mL | Metabolism/transport effects substrate of CYP1A2 (minor), 2A6 (minor), 2B6 (minor), 2C9 (minor), 2D6 (major), and 3A4 (major); it inhibits CYP 1A2 (strong), 2D6 (moderate), and 3A4 (moderate) | Lidocaine may decrease the levels/effects of tramadol
May increase fluoxetine level via inhibition of CYP2D6 |
|
| Midazolam | Heart | 0.105 | Metabolized in the liver and gut via biotransformation mediated by CYP3A4 | N/A | Metabolism/transport effects substrate of CYP2B6 (minor), 3A4 (major) and it inhibits CYP 2C8 (weak), 2C9 (weak), and 3A4 (weak) | The levels/effects of midazolam may be increased by SSRIs
The levels/effects of midazolam may be decreased by carbamazepine and CYP3A4 inducers (strong) |
|
| Carbamazepine | Heart | 5.0 | CYP450
Primarily via CYP3A4
Active metabolites:
Carbamazepine-10,11-epoxide (partly responsible for intoxication) | Therapeutic levels:
4–12 mcg/mL
Toxic level:
>15 mcg/mL | Metabolism/transport effects substrate of CYP2C8 (minor), 3A4 (major),
It induces CYP 1A2 (strong), 2B6 (strong), 2C8 (strong), 2C9 (strong), 2C19 (strong), and 3A4 (strong) | May increase the levels/effects of CNS depressants
The levels/effects of carbamazepine may be increased by CYP3A4 inhibitors and SSRIs (i.e., fluoxetine) |
|
| Hydrocodone | Heart | Free hydrocodone level 0.06 | Liver metabolism by N-demethylation (catalyzed by CYP3A4, 2B6, and 2C19), 0-demethylation (catalyzed by CYP2B6 and 2C19), and 6-keto reduction to the corresponding 6-alpha and 6-beta hydroxyl metabolites
Active metabolites:
Norhydrocodone (major)
Hydromorphone
(minor) | N/A | Metabolism/transport effects substrate of CYP3A4 (major) | May increase the levels/effects of CNS depressants and SSRIs (i.e., fluoxetine) |
|
| Codeine | Heart | Presumptive+ | CYP450
Primarily via CYP2D6, CYP3A4, and UDP-glucuronosyl-transferase 2B7 and 2B4 | Therapeutic: not established
Toxic:
>1.1 mcg/mL | Metabolism/transport effects substrate of CYP2D6 (major) and CYP3A4 (minor)
It inhibits CYP2D6 (weak) | May increase the levels/effects of CNS depressants and SSRIs (i.e., fluoxetine)
May increase fluoxetine level via CYP2D6 inhibition |
|
| Morphine | Heart | Presumptive+ | Liver metabolism by N-demethylation, N-dealkylation, 0-dealkylation, conjugation, and hydrolysis
Active metabolite:
Morphine-3-glucuronide (M3G)
Morphine-6-glucuronide (M6G) | Therapeutic: surgical anesthesia:
65–80 ng/mL
Toxic:
200–5000 ng/mL | Metabolism/ transport effects substrate of CYP2D6 (minor) | May increase the levels/effects of CNS depressants and SSRIs (i.e., fluoxetine) |
|
| Hydromorphone | Heart | Presumptive+ | Extensive liver first-pass metabolism primarily via glucuronidation
Inactive metabolite:
Hydromorphone-3-glucuronide | N/A | Not a significant substrate of inhibitor of CYP450 | May increase the levels/effects of CNS depressants and SSRIs |
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