The case of an 11-year old transplant girl
An 11-year old girl suffered from congenital liver fibrosis (liver disease leading to fibrotic degeneration) underwent liver transplantation. The postoperative course was uneventful and showed normal graft function; however, signs of rejection occurred two weeks after transplantation. Immunological reactions and infections were excluded as the reason of rejection. Testing drug-metabolizing capacity of the donor liver indicated extremely reduced CYP2C9 activity. This enzyme catalyzes the metabolism of the antifungal Mycosyst (fluconazole), the antibacterial Sumetrolim (sulfamethoxazole, trimethoprim) and the Losec (omeprazol) used in ulcus prevention therapy. The results of histopathological examination also confirmed potential drug toxicity. Withdrawal of these drugs was suggested because of functional CYP2C9 deficiency of the graft. In consequence of alterations in medication, the liver graft recovered within one week, and the patient left the hospital. Currently, her days are similar to the lives of other healthy children.
Successful therapy for a 1.5-month old new-born with epileptic symptoms
A 1.5-month old new-born suffered from epilepsy was treated with valproic acid (Convulex); however, some toxic symptoms were observed after two weeks (anemia, thrombocytopenia). The neurologist assumed drug-toxicity and required CYPtesting. CYPtestTM demonstrated genetic defects in CYP2C9 gene (CYP2C9*3/*3) which results non-functional CYP2C9 enzyme. CYP2C9 is responsible for the metabolism of valproic acid. CYP-genotyping results were also confirmed by high blood level of valproic acid which led to toxic symptoms. On the basis of CYPtestTM results, the drug was withdrawn and replaced with an alternative drug (carbamazepine). The patient’s status is stable and her basic disease is successfully controlled by carbamazepine.
Successful medication of a woman with schizoid disorder
CYPtesting a 33-year old woman with schizoid disorder, we demonstrated CYP3A5*1/*3 heterozygous genotype which produces functional CYP3A5 enzyme protein. Functional CYP3A5 enzyme is lacking in more than 90% of Hungarian population which means that most of the population has CYP3A5*3/*3 genotype. Production of functional CYP3A5 enzyme (CYP3A5*1/*3) leads to an increase in CYP3A activity, since the activities of CYP3A5 and CYP3A4 are summed resulting in faster metabolism of certain drugs. Dose increase of these drugs would be required for efficient therapy. The patient in our case was treated with carbamazepine in a daily dose of 400 mg. Since carbamazepine is primarily metabolized by CYP3A enzymes, carbamazepine level in patient’s blood was lower than the therapeutic concentration. Dose increase was proposed to 800 mg which resulted in less pronounced emotional fluctuation, stabilized mood and more balanced lifestyle.
Successful outcome of antihypertension therapy
Gestation hypertension developed at the 21st gestation week of a 35-year old pregnant woman who was treated with methyl-dopa (Dopegyt). On the 23rd gestation week acute hepatitis developed, thus the antihypertensive therapy was changed from methyl-dopa to nifedipine. CYP3A4 enzyme plays a primary role in the metabolism of nifedipine. CYPtestTM indicated poor CYP3A4 metabolizing capacity, therefore reduced nifedipine dose (30 mg daily) was proposed. Blood pressure was successfully controlled with reduced nifedipine therapy. Throughout the gestation period, CYP3A4 expression was followed and nifedipine dosage was adjusted to CYP3A4 status. Finally, a healthy baby was born on the 40th gestation week.