Outline the changes to drug pharmacokinetics and pharmacodynamics that occur at term in pregnancy.

[Click here to toggle visibility of the answers]

College Answer

Answers framed around absorption, distribution, metabolism and excretion performed better. Some brief comments on physiology are required as the basis for pharmacokinetic change, but discussion of physiology that was not then specifically related to pharmacology did not score marks. Specific ‘real life’ examples necessitating change in practice or prescribing were well regarded e.g. reduction in spinal/epidural local anaesthetic dosing. Vague statements about possible or theoretical changes were less well regarded.



  • Absorption:
    • Some factors decrease intestinal absorption:
      • Gastric emptying is delayed
      • Gastric pH is higher
    • Some factors increase intestinal absorption:
      • More complete absorption because of slower gut transit
      • Increased gastrointestinal blood flow
    • Net effect is stable oral bioavailability for most drugs over the course of pregnancy.
    • Increased cardiac output affects changes in skin and muscle blood flow, supposedly increasing the absorption of drugs via subcutaneous and intramuscular routes
    • Increased blood flow speeds up the rate of onset of IV drugs, eg. muscle relaxants and anaesthetic agents
    • Increased pulmonary blood flow and increased respiratory rate allow an increased rate of volatile anaesthetic uptake and therefore decreased time until onset of effect
    • Decreased peridural space due to venous engorgement decreases the required dose of local anaesthetics
  • Distribution:
    • Increased volume of distribution: at the third trimester, blood volume is increased by 50%
    • Decreased protein binding due to diluted serum proteins
    • Delayed release of toxins from fat stores: xenobiotics are laid down together with increasing fat stores in early pregnancy, and then mobilised during later stages and the postpartum period
    • Increased fatty acid levels: they will compete with drugs for binding sites on albumin
    • Increased sensitivity to local anaesthetics (due to decreased α1-glycoprotein levels)
  • Metabolism:
    • Altered hepatic clearance:
      • circulating hormones can induce or inhibit metabolic enzymes.
      • Progesterone induces enzymes
      • Oestrogen competes for metabolic enzymes (eg. with vecuronium and rocuronium)
    • Decreased plasma cholinesterase activity (though this does not result in increased duration of action for suxamethonium)
    • The placenta has liver-like biotransformative enzymes, although these are not equivalent to the liver in their metabolic capacity, and probably not an effective protection for the foetus.
  • Elimination:
    • Renal clearance of drugs increases mainly due to increased glomerular filtration rate. Drugs cleared solely by glomerular filtration are most affected (eg. cephazolin, clindamycin)
    • Tubular resorption of substances also increases, counteracting the increased GFR
    • Thus, renal clearance for any specific drug is difficult to predict - eg. clearance doubles for lithium, increases 30% for digoxin, and only increases 12% for atenolol  (Feghali et al, 2015)
    • Hepatobiliary clearance of drugs is reduced by the cholestatic effects of oestrogen


  • Increased sensitivity to volatile anaesthetics (decreased MAC)
  • Increased sensitivity to IV anaesthetics
  • Increased sensitivity to local anaesthetics
  • Changed therapeutic indices due to concerns regarding foetal damage and teratogenicity



Anderson, Gail D. "Pregnancy-induced changes in pharmacokinetics." Clinical pharmacokinetics 44.10 (2005): 989-1008.

Costantine, Maged. "Physiologic and pharmacokinetic changes in pregnancy." Frontiers in pharmacology 5 (2014): 65.

Mattison, Donald, ed. Clinical pharmacology during pregnancy. Academic Press, 2012.

Mirkin, Bernard L. "Maternal and fetal distribution of drugs in pregnancy." Clinical Pharmacology & Therapeutics 14.4part2 (1973): 643-647.

Ansari, Jessica, et al. "Pharmacokinetics and pharmacodynamics of drugs commonly used in pregnancy and parturition." Anesthesia & Analgesia 122.3 (2016): 786-804.

Philipson, Agneta. "Pharmacokinetics of ampicillin during pregnancy." Journal of Infectious Diseases 136.3 (1977): 370-376.

Lander, C. M., et al. "Bioavailability and pharmacokinetics of phenytoin during pregnancy." European journal of clinical pharmacology 27.1 (1984): 105-110.

Feghali, Maisa, Raman Venkataramanan, and Steve Caritis. "Pharmacokinetics of drugs in pregnancy." Seminars in perinatology. Vol. 39. No. 7. WB Saunders, 2015.

O'Hare, M. F., et al. "Pharmacokinetics of sotalol during pregnancy." European journal of clinical pharmacology 24.4 (1983): 521-524.

Casele, Holly L., et al. "Changes in the pharmacokinetics of the low-molecular-weight heparin enoxaparin sodium during pregnancy." American journal of obstetrics and gynecology181.5 (1999): 1113-1117.

Krauer, Beatrice, and F. Krauer. "Drug kinetics in pregnancy." Clinical pharmacokinetics 2.3 (1977): 167-181.

Gerdin, Eva, et al. "Maternal kinetics of morphine during labour." Journal of Perinatal Medicine-Official Journal of the WAPM 18.6 (1990): 479-487.

Mucklow, J. C. "The fate of drugs in pregnancy." Clinics in obstetrics and gynaecology 13.2 (1986): 161-175.

Gin, Tony, and M. T. Chan. "Decreased minimum alveolar concentration of isoflurane in pregnant humans." Anesthesiology 81.4 (1994): 829-832.

Palahniuk, Richard J., Sol M. Shnider, and E. I. Eger. "Pregnancy decreases the requirement for inhaled anesthetic agents." Anesthesiology 41.1 (1974): 82-83.

Gin, Tony, et al. "Decreased thiopental requirements in early pregnancy." Anesthesiology: The Journal of the American Society of Anesthesiologists 86.1 (1997): 73-78.

Baraka, Anis, et al. "Onset of vecuronium neuromuscular block is more rapid in patients undergoing caesarean section." Canadian journal of anaesthesia 39.2 (1992): 135-138.

Khuenl-Brady, Karin S., et al. "Comparison of vecuronium-and atracurium-induced neuromuscular blockade in postpartum and nonpregnant patients." Anesthesia and analgesia 72.1 (1991): 110-113.

Walker, F. O., and S. Z. Lysak. "Pregnancy increases median nerve susceptibility to lidocaine." Anesthesiology 72.6 (1990): 962-965.

Tsen, Lawrence C., et al. "Measurements of maternal protein binding of bupivacaine throughout pregnancy." Anesthesia & Analgesia 89.4 (1999): 965.

Morishima, Hisayo O., et al. "Bupivacaine toxicity in pregnant and nonpregnant ewes." Anesthesiology 63.2 (1985): 134-139.

Bologa, M. O. N. I. C. A., et al. "Pregnancy-induced changes in drug metabolism in epileptic women." Journal of Pharmacology and Experimental Therapeutics 257.2 (1991): 735-740.

Lander, Cecilie M., et al. "Plasma anticonvulsant concentrations during pregnancy." Neurology 27.2 (1977): 128-128.

Assali, N. S., and Harry Prystowsky. "Studies on autonomic blockade. I. Comparison between the effects of tetraethylammonium chloride (TEAC) and high selective spinal anesthesia on blood pressure of normal and toxemic pregnancy." The Journal of clinical investigation 29.10 (1950): 1354-1366.

Pariente, Gali, et al. "Pregnancy-associated changes in pharmacokinetics: a systematic review." PLoS medicine 13.11 (2016): e1002160.

Dawes, Matthew, and Philip J. Chowienczyk. "Pharmacokinetics in pregnancy." Best practice & research Clinical obstetrics & gynaecology 15.6 (2001): 819-826.

Denti, Paolo, et al. "Population pharmacokinetics of rifampin in pregnant women with tuberculosis and HIV coinfection in Soweto, South Africa." Antimicrobial agents and chemotherapy 60.3 (2016): 1234-1241.