Theophylline Flashcards
Theophylline Indications
Bronchodilator (not used much) to manage COPD; asthma; bronchitis; emphysema
Pediatrics: Prevention of apnea/bradycardia (premature)
Adverse Effects Theophylline
Why does theophylline require TDM?
Possible Non-Linear - Michaelis Menton
Wide interpt variability
Good corellation between CP and response
Narrow Therapeutic Index
Bioavilability Theophylline
Well absorbed – high F
Some formulations show pH dependent dissolution (weak acid, pKa = 8.7) – slower than expected
Rate of absorption theophylline affecetd by:
Rate affected by:
Food; co-administered antacids
Time of day
Note: Lag time between administration and effect
Oral formulations theophylline
Rapid-release tablet or liquid solution
F = 1; tmax = 1.4 h
Sustained-release tablet
Variable absorption rates (tmax high) ; high F
DO NOT substitute S-R products
Vd Theophylline Obese
Obese: use IBW in PK calculations (distributing into lean body mass; not going into adipose)
Tissue Distribution Theophylline
Lung:
Delayed distribution
CSF:
Useful to treat apnea in premature
CNS toxicity at high doses
Theophylline Metabolism
Liver metabolism (85-90%)
CYP1A2
↑Drug-drug interactions
Low Extraction ratio
fu(b) and Clint principal determinants of hepatic cl
Theophylline Renal Clerance
10-15% of adults
50% in neonates - CYP 1A2 Immature
Compare once-a-day products?
Theophylline Cls is effected by…..
Does Danny Actually Carry Diesal Can Tony Obtain Cigs Immediately
Switching theophylline IV to oral
Changing from IV to oral sustained-release product first administer the oral SR product and discontinue IV 1 -2 hours later
Theophylline Css occurs when….
For continuous infusion take sample >24 h after MD initiation
CSS.min occurs at 3 – 5 half-lives if a LD given
Theophylline t1/2 = 8 – 9 h so sample at ~24 h after MD initiated
For TR, CSS.min sample is taken 1 hour before the next dose for oral (tablet, liquid, SR products) and intermittent injection.
