Pharmacokinetics of theophylline in hepatic disease.

The disposition of theophylline was examined in eight male cirrhotic (six proven by biopsy) patients without heart failure. An oral dose of 100 mg of theophylline per square meter of surface area was administered, and samples of serum and saliva were collected from 0 to 60 hours and were assayed by high-pressure liquid chromatographic techniques. Controls were 57 young normal subjects and 25 age-matched patients. The body clearance of theophylline in cirrhotic patients was low, averaging 18.8 +/- 11.3 ml/kg/hr (+/- SD) vs 53.7 +/- 19.3 and 63.0 +/- 28.5 ml/kg/hr in the control patients and the normal subjects, respectively. The half-life of theophylline in cirrhotic patients was prolonged wiht a mean of 28.8 +/- 14.3 hours compared to 6.0 +/- 2.1 hours in normal subjects. Patients with cirrhosis proven by biopsy had significantly lower values for body clearance and longer half-lives than subjects without biopsies. The values for body clearance correlated well with the serum level of bilirubin (r = -0.81) and the serum level of bile acids (r = -0.81). The slow and variable metabolism in cirrhotic patients necessitates a reduction in the maintenance dosage of aminophylline to 0.20 to 0.45 mg/kg/hr and monitoring of the serum level during therapy.

Beneficial effect of a pharmacist refill evaluation clinic.

A study of 32 patients attending a pharmacist-run clinic was performed. This pharmacist refill evaluation clinic (PREC) assesses the continuation of maintenance drug therapy and is an alternative to the physician's clinic. This study evaluated total time spent at the clinic, reasons for refill requests, number of refills requested, number of requested refills approved, and number of physician consults and referrals required. The total clinic visit time at the PREC was 60 +/- 35.9 minutes versus a total time required at physicians clinic of 129 +/- 115.2 minutes. Of the patients treated at the PREC, 90.6% required no physician consult or referral. An estimated $135 savings in drug cost was approximated by the clinic during this small sample (a 30-day study), plus a difference in clinic fee that would amount to $1120 not including the difference in the pharmacist and physician's salaries. Other contributions attributed to this clinic were better patient compliance, accurate documentation of medication records, drug abuse surveillance, and drug therapy efficacy.

Fatal seizures after flumazenil administration in a patient with mixed overdose.

OBJECTIVE: To report a fatal case of refractory status epilepticus precipitated by flumazenil use in a mixed benzodiazepine-tricyclic antidepressant overdose. CASE SUMMARY: A 39-year-old woman was brought to the emergency room (ER) in a stupor from a suspected suicidal overdose of an unknown mixture of drugs. Past medical history included seizures and psychiatric disorders managed with benzodiazepine and tricyclic antidepressants. Initial ER electrocardiogram showed a QRS interval of 136 milliseconds. The patient developed refractory seizures after being given flumazenil. Lorazepam, phenytoin, and phenobarbital were administered; however, seizures persisted for 4 hours, resulting in rhabdomyolysis, acute renal failure, severe brain damage, and death. DISCUSSION: Flumazenil should be used with caution in patients with chronic benzodiazepine use, prior seizure history, or when a mixed overdose is suspected. Flumazenil may unmask tricyclic antidepressant-induced seizures by antagonizing the antiepileptic effect of concomitantly ingested benzodiazepine. In this patient seizures occurred within two minutes of flumazenil administration. As benzodiazepine-induced central nervous system depression is rarely life-threatening, the use of flumazenil must be balanced against potential risk. CONCLUSIONS: Seizure risk factors should be assessed in all patients in whom flumazenil use is considered. If risk factors are present, the benefit of flumazenil use is outweighed by the potential risk. If flumazenil is used, resulting seizures may require larger doses of benzodiazepine.

Amiodarone interaction with lidocaine.

We report a case of lidocaine toxicity with seizures that appears to represent a drug interaction with amiodarone. A toxic lidocaine level and reduced lidocaine clearance were documented 65 h after amiodarone was added to the treatment regimen. This is the first report of increased levels and serious clinical toxicity of lidocaine due to amiodarone. The mechanism appears to be altered hepatic metabolism of lidocaine caused by amiodarone.