ABSTRACT
Valproic acid is an anticonvulsant drug known to inhibit the glucuronidation of zidovudine (AZT) in human liver microsomes. Zidovudine is metabolized by glucuronidation to the inactive 5'-glucuronide with a short plasma half-life (1.0 +/- 0.2 hour). This case presentation confirms that valproic acid inhibits glucuronidation in vivo, and this is the first documented observation of increased cerebrospinal fluid levels of zidovudine because of an interaction with valproic acid in a patient with acquired immune deficiency syndrome (AIDS). The peak plasma AZT level for the control period was 119 ng/mL, which increased almost 3-fold to 344 ng/mL with valproic acid (1.5 g/day). The plasma AZT trough was 47 ng/mL, which also increased almost 3-fold to 124 ng/mL with valproic acid. The molar ratio of plasma 5'-glucuronide/AZT at the peak was reduced from 1.77 (control) to 1.07 with valproic acid. The 5'-glucuronide/AZT ratio at the trough was reduced markedly from 5.0 (control) to 0.93 with valproic acid, suggesting in vivo inhibition of glucuronidation. Cerebrospinal AZT levels, drawn 30 minutes after peak plasma levels, increased from 27 ng/mL for the control to 47 ng/mL with valproic acid, which paralleled the change in peak plasma concentrations. This interaction with valproic acid may contribute to higher AZT levels in the brains of patients with human immunodeficiency virus-related (HIV) encephalopathy.
Subject(s)
AIDS Dementia Complex/cerebrospinal fluid , AIDS Dementia Complex/drug therapy , Acquired Immunodeficiency Syndrome/cerebrospinal fluid , Acquired Immunodeficiency Syndrome/drug therapy , Anticonvulsants/pharmacology , Valproic Acid/pharmacology , Zidovudine/cerebrospinal fluid , AIDS Dementia Complex/blood , Acquired Immunodeficiency Syndrome/blood , Adult , Anticonvulsants/administration & dosage , Drug Interactions , Humans , Kinetics , Male , Valproic Acid/administration & dosage , Zidovudine/administration & dosage , Zidovudine/analogs & derivatives , Zidovudine/bloodABSTRACT
We report a case of cycloserine-induced Stevens-Johnson syndrome (SJS) in a 38-year-old male with the acquired immune deficiency syndrome (AIDS) and multidrug resistant tuberculosis (MDR-TB). The patient developed a cutaneous reaction after 60 days of therapy with ofloxacin, streptomycin (SM), pyrazinamide (PZA), ethambutol (EMB), and cycloserine (CSN). All drugs were stopped and the rash improved. Due to the severity of his disease, anti-tuberculosis drugs were resumed, one at a time. The patient developed a recurrent rash consistent with SJS, which began when CSN was restarted. CSN was stopped and the SJS began to gradually resolve with palliative treatment despite continuation of the other anti-tuberculosis drugs. However, the patient's overall condition gradually deteriorated and he died. To our knowledge, this is the first case of probable CSN-related SJS.
Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antibiotics, Antitubercular/adverse effects , Cycloserine/adverse effects , Stevens-Johnson Syndrome/chemically induced , Tuberculosis, Multidrug-Resistant/drug therapy , Adult , Antibiotics, Antitubercular/therapeutic use , Cycloserine/therapeutic use , Drug Therapy, Combination , Exanthema/chemically induced , Fatal Outcome , Humans , Male , Stevens-Johnson Syndrome/diagnosisABSTRACT
To study its safety and efficacy in treating cytomegalovirus (CMV) retinitis, an AIDS patient received an intravitreal injection of liposome encapsulated ganciclovir in the right eye. The left eye served as a control, receiving intravitreal free ganciclovir. The right eye showed no retinal haemorrhages or detachment; however, vision declined initially, stabilising later. Weekly examination showed neither progression of the CMV retinitis nor new lesions in the right eye. The left eye showed reactivation of old CMV retinitis. Liposome encapsulated ganciclovir reduced the number of intravitreal injections, stabilising CMV retinitis, and warrants further study.
