ADME Flashcards
Tamoxifen absorption
- Rapid and complete oral absorption
- Peak in 5 hours
- Css reached in 3-4 weeks, or up to 16 weeks
Tamoxifen distribution
- Highly plasma protein bound
- High Vd (50-60 L/kg)
- Good distribution to the breast, uterus, liver, kidneys, lungs, pancreas, ovaries (up to 10x higher in breast than blood)
Tamoxifen metabolism
- CYP2D6 (hydroxylation) & CYP3A4 (N-demethylation)
- Phase 2 (sulfation, glucuronidation)
Tamoxifen elimination
- Similar CL as CrCL
- T1/2 of 5-7 days
- Feces
- Negligible urine
Pembrolizumab absorption
- IV 200 mg as a slow infusion, every 3 weeks
- May reach Css in 19 weeks
Pembrolizumab distribution
- Small Vd of 7 L
- Not bound to albumin in any specific manner
Pembrolizumab metabolism
- Non-specific protein catabolism
Pembrolizumab elimination
- Unknown on the routes
- T1/2 of 27 days
- Factors affecting CL = albumin/bilirubin levels, type of cancer, gender
Leuprorelin absorption
- SC/IM administration as a single depot dose
- Cmax reached in 1-3 hours
- Css reached in 4 weeks
Leuprorelin distribution
- ~45% bound to albumin
- Unclear Vd
Leuprorelin metabolism
- Proteolytic degradation pathways
Leuprorelin elimination
- T1/2 of 3 hours
- Non-significant by the urine or feces
Bicalutamide absorption
- PO once daily
Bicalutamide distribution
- Highly albumin bound
Bicalutamide metabolism
- S: glucuronidation
- R: hydroxylation by 3A4, glucuronidation
Bicalutamide elimination
- T1/2 of 6 days
- Excreted in bile & urine
Metformin absorption
- Taken orally
- Duration of action: 8-12 hours
- Onset within days, max effect up to 2 weeks
Metformin distribution
- Not bound to plasma protein
Metformin metabolism
- Nil liver metabolism
Metformin elimination
- T1/2 of 3 hours
- Mostly excreted unchanged in the urine
Glipizide absorption
- Well absorbed
- Absorption is delayed with food
- Onset of action: 0.5 hours
- Duration of action: 12-24 hours
Glipizide distribution
- Highly bound to albumin
Glipizide metabolism
- Hydroxylation in the liver
Glipizide elimination
- T1/2 of 4 hours
- < 10% excreted unchanged in the urine & feces
- Action prolonged in renal impairments
Sitagliptin absorption
- Relatively good oral bioavailability
Sitagliptin metabolism
- Low liver metabolism
Sitagliptin elimination
- T1/2 of 10-12 hours
- 80% excreted unchanged in the urine
Liraglutide absorption
- Daily SC dosing, steady state daily maintenance dose of 3 mg
- 55% bioavailability
Liraglutide distribution
- C16 FA chain binds to albumin
Liraglutide metabolism
- Non-specific catabolism
Liraglutide elimination
- T1/2 of 13 hours
- Negligible in urine & feces
Empagliflozin absorption
- 60-80% bioavailability
Empagliflozin distribution
- Highly bound to albumin
Empagliflozin metabolism
- Glucuronidation
Empagliflozin elimination
- T1/2 of 12 hours
- 40% in feces, 50% in urine
Carbimazole absorption
- Once daily dosing
- Inhibitory effect achieved within 12 hours
- Effect may be delayed to 4-6 months
Carbimazole distribution
- Methimazole concentrates well in the thyroid gland
- No plasma protein binding
- Produces the inhibition of thyroid hormone production in 12 hours, but full effect takes up to 3-6 weeks
- Max effect take 4-6 months
Carbimazole metabolism
- CYP450 & FMO
Carbimazole elimination
- T1/2 of 4-6 hours but clinical effect lasts a day
- Metabolites excreted 90% in urine
Levothyroxine absorption
- Erratic absorption
- Taken 30-60 mins before food
- Absorption affected by polyvalent cations, increased gastric pH, fibres, GI motility
- Onset of action 3-5 days, 6-8 hours (IV)
- Symptomatic relief in 2-3 weeks
Levothyroxine distribution
- Highly plasma protein bound
Levothyroxine metabolism
- Deiodination by liver, kidneys and peripheral tissues
- Glucuronidation & sulfation by liver
Levothyroxine elimination
- T1/2 of 7 days
- Excreted in urine, feces, and metabolites in bile
Rapid acting insulin
- Onset 15-30 mins
- Peak: 1-2 hours
Short acting insulin
- Onset 30-60 mins
- Peak 2-4 hours
Intermediate acting insulin
- Onset 1-2 hours
- Peak 6-12 hours
- Duration of action: 10-16 hours
Detemir
- Onset 1-2 hours
- Hill
- Duration of action: 12 hours or up to 20-24 hours
Glargine U-100
- Onset 1-2 hours
- No peak
Duration of action: 24 hours
Tamsulosin absorption
- Once daily 0.4 mcg
- Onset within days to weeks
Tamsulosin distribution
- Highly bound to plasma proteins
- Small Vd of 0.2 L/kg
Tamsulosin metabolism
- CYP2D6 & 3A4
Tamsulosin elimination
- T1/2 of 10-15 hours
- Metabolites excreted in urine
Finasteride absorption
- Orally 5 mg once daily
- Relatively low F of 0.65
- Delayed onset, up to 6-12 months to observe clinical improvement
- Nil dose adjustment
Finasteride distribution
- Highly bound to plasma proteins
Finasteride metabolism
- CYP3A4
Finasteride elimination
- T1/2 of 6 hours
- 50% excreted unchanged in feces
- Metabolites in urine & feces
Sildenafil absorption
- Low F of 0.4
- Onset 30-60 mins
- Duration of action 12 hours
Sildenafil distribution
- Highly plasma protein bound
Sildenafil metabolism
- Major: CYP3A4
- Minor: CYP2C9
Sildenafil elimination
- T1/2 of 4 hours
- Metabolites in feces
Ethinyl estradiol absorption
- Onset 30-60 mins
- Relatively low F of 0.4
Ethinyl estradiol distribution
- Highly bound to plasma proteins
Ethinyl estradiol metabolism
- Phase 1: Hydroxylation by CYP3A4
- Phase 2: Glucuronidation & sulfation
- Ethinyl estradiol sulfate undergoes enterohepatic recirculation
Ethinyl estradiol elimination
- T1/2 of 13-27 hours
- Urine & feces
Norethindrone absorption
- Relatively low F of 0.6
Norethindrone distribution
- Highly bound to plasma proteins
Norethindrone metabolism
- Phase 1: Reduction
- Phase 2: Glucuronidation, sulfation
- May be metabolised into EE
Norethindrone elimination
- T1/2 of 8 hours
- Urine & feces
