Table 3.
Clinical pharmacokinetic and pharmacodynamic data for selected drugs in pregnancy.
| Drugs | Metabolism/elimination path | Maternal PK in pregnancy | Fetal:maternal ratio | PK-PD |
|---|---|---|---|---|
| Analgesics | ||||
| Acetaminophen50 | Hepatic UGT1A, SULT1A, CYP2E1, and acetyltransferase | 50% ↑ Clearance, 140% ↑ glucuronide/parent, 80% ↑ oxidatives/parent, and ↔ clearance for acetaminophen sulfate | l.0 | Concentration–toxicity |
| Antiepileptic | ||||
| Lamotrigine52–54,58–65 | Hepatic UGT1A3 and 1A4 | 65–164% ↑ Clearance, ↑ metabolite/parent, and ↓ concentration | 1.2 | ↑ Seizure frequency |
| Phenytoin54 | Hepatic CYP2C9 | 117% ↑ Clearance, altered plasma protein binding, ↓ total concentration, and ↔ unbound concentration | NA | NA |
| Levetiracetam61,66,67 | 66% Unchanged via renal | ↑ Renal clearance and ↓ concentration | 1.1 | NA |
| Antihypertensive | ||||
| Clonidine68,69 | Hepatic CYP2D6 | 80% ↑ Total clearance, ↔ renal clearance | 1.0 | NA |
| Labetalol26,70 | Hepatic UGT1A1 | ↔ or ↑ clearance | 0.5 | Concentration–efficacy |
| Atenolol71 | Renal excretion | ↑ Renal clearance | NA | NA |
| Antidiabetes | ||||
| Glyburide55,56 | Hepatic CYP2C9 and 3A | ↑ Clearance and ↓ concentration | 0.7 | NA |
| Metformin72 | Renal excretion and minimal metabolism | ↔ or ↑ Clearance | 0.7 | NA |
| Antiretrovirals | ||||
| Indinavir73,74 | Hepatic CYP3A | 68% ↓ Exposure | 0.12 | No correlation |
| Lopinavir/ritonavir75–83 | CYP3A | 58% ↑ Clearance, ↓ exposure, and ↔ unbound concentration | 0.2 | Concentration–toxicity |
| Nelfinavir82–85 | Hepatic CYP3A and 2C19 | 100% ↑ Clearance, ↓ exposure, ↓ total concentration, and ↓ unbound concentration | 0.3–0.4 | Concentration–efficacy |
| Nevirapine83,86,87 | Hepatic CYP3A4 and 2B6 | ↔ Or ↑ clearance and 22% ↓ exposure | 0.8 | NA |
| Efavirenz75,88 | Hepatic CYP3A and 2B6 | ↔ Clearance and ↓ concentration | 0.5 | NA |
| Tenofovir89–90 | Renal filtration and active tubular secretion | ↑ Clearance | 0.6 | NA |
| Lamivudine91 | 71% Unchanged via renal | 22% ↑ Clearance and ↔ pk | 0.86–5 | NA |
| Emtricitabine92 | UGT | 21% ↑ Clearance | 1.0 | NA |
| Anti-influenza | ||||
| Oseltamivir93 | Hepatic esterases and renal filtration and secretion | ↔ pk For oseltamivir and 44% ↑ clearance for oseltamivir carboxylate | 0.4 | NA |
| Antifungal | ||||
| Metronidazole6 | Hepatic | ↔ pk | 0.3–2 | NA |
| Antimalarial | ||||
| Sulfadoxine-pyrimethamine94 | N-acetyltransferase | 67% ↑ Clearance | NA | NA |
| SSRIs | ||||
| Sertraline95 | Hepatic CYP2C9, 2C19, 2D6, 3A, and UGT1A1 | ↔ pk | 0.67 | NA |
| Fluoxetine | Hepatic CYP2D6 | 2 6 ↑ Metabolite/parent | 0.67 | NA |
| Immunosuppressants | ||||
| Tacrolimus13,14,96 | Hepatic CYP3A | 39% ↑ Clearance, ↓ whole-blood conc., and 1.9–2.0 ↑ unbound concentration | 0.71 | NA |
| Opioid substitute | ||||
| Methadone97 | Hepatic CYP2B6, 2C19, 2C9, 2D6, and 3A4 | 90% ↑ Clearance | NA | NA |
| Antineoplastic agents | ||||
| Doxorubicin98–100 | Hepatic CYP2D6, 3A4, and P-glycoprotein | ↑ or ↓ Clearance | NA | NA |
| Epirubicin98,99 | Hepatic UGT2B7 | 43% ↑ Clearance | NA | NA |
| Paclitaxel98,99 | Hepatic CYP2C8 and 3A4 | 21% ↑ Clearance | NA | NA |
Note: ↑, increase; ↓, decrease; ↔, no change; CYP, cytochrome P450; UGT, UDP-glucuronosyltransferase; SSRIs, selective serotonin reuptake inhibitors; TDM, therapeutic drug monitoring; PK, pharmacokinetics; PD, pharmacodynamics; NA, not available.