Penetration of Clindamycin and Its Metabolite N -Demethylclindamycin into Cerebrospinal Fluid following Intravenous Infusion of Clindamycin Phosphate in Patients with AIDS

Abstract

Clindamycin, which is usually used in combination with pyrimethamine, has been proven effective in the treatment of cerebral toxoplasmosis in human immunodeficiency virus-infected patients. However, it is not known if clindamycin achieves inhibitory concentrations at the site of infection. Also, it has been hypothesized that the activity of clindamycin against Toxoplasma gondiimay be due, at least in part, to a metabolite. We evaluated the penetration of clindamycin and its major metabolite,N-demethylclindamycin (NDC), into cerebrospinal fluid (CSF) of AIDS patients undergoing lumbar puncture for diagnostic purposes. A single, 1,200-mg dose of clindamycin was administered as a 45-min intravenous infusion beginning at 1.5 or 2.5 h before CSF sampling. The concentrations of clindamycin in CSF ranged from 0.091 to 0.429 mg/liter at 1.5 h and from 0.120 to 0.283 mg/liter at 2.5 h following the beginning of the infusion. The concentrations of clindamycin in CSF were well above the 50% inhibitory concentration of 0.001 mg/liter and the parasiticidal concentration of 0.006 mg/liter. NDC was undetectable both in plasma and in CSF. Our study provides a pharmacokinetic rationale for the clinical efficacy of clindamycin in the treatment of cerebral toxoplasmosis.

Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria

“…It has been suggested that time-dependent antimicrobial agents should remain above the MIC of pathogens for at least three malaria cycle of seven days. Unlike fosmidomycin, recent studies have suggested that clindamycin displays concentration-dependent bacteriocidal activity [17,29] while exhibiting an in vitro post antibiotic effect (PAE) for certain period. In vivo , the PAE is generally longer and due to effects such as post antibiotic leukocyte enhancement and post-antibiotic sub-MIC effect.…”

Development of a Pediatric Physiologically-Based Pharmacokinetic Model of Clindamycin Using Opportunistic Pharmacokinetic Data

“…We excluded data obtained using microbiologic assay techniques that may not have reliably distinguished clindamycin from clindamycin metabolite concentrations. To provide the concentration time data for the adult PBPK model development, we selected 3 adult clindamycin PK studies that were most appropriate based on route of administration, study participant demographics and clinical characteristics, and bioanalytical method used (Supplementary Table 1) (13-15). We used the software Plot Digitizer® (version 2.6.6) to extract the concentration versus time data.…”

Central nervous system toxoplasmosis in HIV pathogenesis, diagnosis, and therapy

“…In that study, 8 of 49 patients experienced dose-limiting toxic effects, most commonly rash. Gutti et al looked at penetration of clindamycin and its metabolite into cerebrospinal fluid in AIDS patients, and found that the concentrations of clindamycin in CSF are well above the 50% inhibitory concentrat io n of 0.0 01 m g p er lite r and the para sit i cidal concentration of 0.006 mg per liter [28].…”