Pharmacokinetics: Theophylline Allie Punke (apunke@uthsc.edu)

The Basics How much theophylline does aminophylline contain? What body weight do we use? What Vd should we “assume” for testing purposes? What enzymes metabolize theophylline? Vd=0.5 L/kg *USE ADJUSTED BODY WEIGHT IF >1.5*IBW. Look at equation for adjusted body weight in your notes. It’s slightly different than what we’ve used previously. CYP1A2 and CYP2E1

The Basics What is the “target” level? When measuring a blood level, are we measuring theophylline or aminophylline? If a patient receives the SR (once daily administration), what is something that we may be concerned about occurring? ~10 (5-15) Theophylline Possibly releasing too much theophylline…to cause toxicity.

The Basics—True or False Premature infants, adults with hepatic cirrhosis, and those with uncorrected acidosis have a lower Vd. Protein binding needs to be accounted for to adjust theophylline levels. For every 1 mg/kg increase in dose, the serum concentration should increase by 4 mg/kg Theophylline is metabolized by CYP1A2 and CYP2E1 to mostly inactive metabolites. In adults, a common metabolite occurs by methylation of theophylline. False 2. False 3. False 4. True 5. False…common in infants.

The Basics—True or False Methylation is more advanced in infants caffeine.

ADME of Theophylline CYP1A2 exhibits increased or decreased activity in children? Theophylline is primarily dependent on the liver or kidney for elimination in children? What about adults? By the 1st month of age, do they experience increased or decreased clearance? Increased Kidney Increased (still increased in adolescents, but then decreases in adults and geriatrics)

The Basics—True or False *Main point that I wanted to emphasize is that in infants, it’s more dependent on kidney vs in adults, it’s more dependent on liver. AND in infants a major metabolite is caffeine, which is not true in adults.

Interactions… Increased or Decreased clearance with these disease states: Viral Illness Pneumonia Diet (high protein, low carbs) Smoking Increased or Decreased clearance with these drugs: Erythromycin Carbamazepine Cimetidine

Application GP, a 17 year old (132 kg, 64 in) needs to be loaded with aminophylline. What loading dose should he receive to achieve a concentration of 13? Assume a normal Vd. 1. What body weight should we use? 2. Calculate LD for theophylline. 3. Convert to aminophylline. IBW=59.2 kg Adjusted BW=77.4 kg…need to use adjusted BW since actual body weight is 1.5*IBW LD theo=503 mg LD amino=630 mg

Application GP, a 12 year old child (132 kg, 64 in) needs to be loaded with aminophylline. He has been taking theophylline at home chronically for several years. After your recommendation to give him the loading dose, the level comes back 9 mg/L. What is his Vd? C=D/V 9 mg/L=6.5 mg/kg theo adjusted body weight/V V=0.72 L/kg

Application GP, a 12 year old child (132 kg, 64 in) needs to be loaded with aminophylline. What loading dose of aminophylline should he receive to achieve a concentration of 13? Assume a normal Vd. He has been taking theophylline at home chronically for several years. 1. What information would you like? 2. His serum concentration was 1. Calculate partial loading dose. 3. What other times should we draw a level? Should draw level. Partial loading dose=0.5L/kg*77.4 kg (adjusted body weight)*(13-1) Answer on next slide

Application

Application BP, a 20 kg patient, is just being started on theophylline for an asthma exacerbation. She is also on cimetidine. Do her LD and MD need to be adjusted due to a possible drug interaction? A. LD and MD should both be decreased. B. LD and MD should both be increased. C. LD should be increased, but MD should not be adjusted. D. LD should not be adjusted, but MD should be decreased. D

Application TC, a 20 kg patient, has been receiving a continuous infusion of aminophylline @ 1.5 mg/kg/hr for about 2 days. Assume that the patient is responding well to treatment. What dose and timing you recommend to switch her from IV to PO SR theophylline? What about to immediate release theophylline? 576 mg theophylline..wait 2 hours after the oral dose is given before stopping IV aminophylline Immediate release…may just be able to shut off IV when give oral, or maybe wait 15-30 minutes after give oral to shut off IV

Application In a patient receiving theophylline, the serum concentration was 20. What are some signs/symptoms that you would expect the patient to be experiencing? In your notes

Application The medical team wants to increase the dose of theophylline from 750 mg to 1000 mg. What do you think about this recommendation? Percent change= 33%. Increase by no more than 20% at a time.

Summary Remember the basic numbers for theophylline Know how to convert from aminophylline  theophylline Recognize when you should adjust for a patient’s body weight Remember that the blood concentration is always theophylline

Questions? Enjoy your weekend!