Apparent volume of distribution=Dose/Plasma drug concentration

High Vd :drug binds more to tissue

Low Vd: drug bound more to blood

 4 *T1/2 to eliminate drug

T1/2 of Caffeine is much longer during pregnancy

Vd of caffeine remain the same during pregnancy

P450 changes during pregnancy, making caffein harder to eliminate

Fetal Exposure to Drug

Rapid diffusion for single/multy drug: drug move quickly to fetus and equilibrate

Slow diffusion for single drug: drug accumulate in fetus for period of time then eliminate and transport back to the mother via plasma.

Slow diffusion for multi drug: equilibration of concentration is slow.

Thalidomide: associated with irreversible malformation of limbs (phocomelia)

POP (persistent organic pollutant) in breast milk. recall that lipid soluble drug can be easily transported in breast milk.

NSAID: block prostaglandin E1 production which inhibit labour and close ductus arteriosis

  Prostaglandin E1 induce labout and maintain the hold open.

Drug Absorption changes 

High gastric pH

slow gastric emptying increase absorption

GI flora

Increased skin permeability increase absorption

Drug Distribution

fat/water ratio

infants have high body water content and low fat.

fraction of lipophilic drug in fatty tissues is low

Drug elimination

Renal and hepatic fxn less efficient in baby

drug effect prolonged and accumulation may occur.

Genetamicin:  9 times longer T1/2 in NB than adult

Phase 1 (oxidation, hydroxylation, dealkylation, deamination)

NB lack CYP 450 that demethylate caffeine

Phase 2 (conjugation)

Acetaminophen: converted to glucoronide conjugates and sulphate conjugate. NB can only do sulfation.

Chloramphenicol: antibac for CNS infection, immaturity of glucuronidation in NB can lead to accumulation and toxicity (gray baby syndrome due to lack of O2)

Bilirubin: deficiency of glucuronide transferase lead to jaundice.