title: Pharmacokinetics and cerebrospinal fluid penetration of norvancomycin in Chinese adult patients.
abstract: Norvancomycin is an antibiotic that has been approved for the treatment of infections caused by antibiotic-resistant Gram-positive bacteria and has been used in China for more than a decade. However, the cerebrospinal fluid (CSF) penetration of norvancomycin has not been evaluated. The aims of the study were (i) to investigate the pharmacokinetics and CSF penetration of norvancomycin in meningitis and non-meningitis patients and (ii) to recommend favourable dosing regimens in meningitis patients. Twenty adult patients (ten with meningitis and ten without meningitis) requiring norvancomycin treatment were enrolled. All patients received a norvancomycin regimen of 800 mg every 12 h. Blood and CSF samples were consecutively collected up to 12 h after the end of the fourth 60-min infusion. Norvancomycin concentrations both in serum and CSF were measured using a high-performance liquid chromatography (HPLC) assay. CSF penetration of norvancomycin was evaluated by calculating the CSF/serum ratio. Mean norvancomycin serum trough levels were 9.9 ± 1.44 µg/mL in patients with meningitis and 10.08 ± 1.12 µg/mL in patients without meningitis (P > 0.05). In addition, norvancomycin penetrated into the inflamed meninges, with mean CSF concentrations of 3.93-10.52 µg/mL and mean CSF/serum ratios of 0.18-0.43, both of which were significantly higher than in patients without meningitis (P <0.05). These results suggest that norvancomycin has higher CSF penetration in patients with meningitis compared with other groups and that norvancomycin is effective in treating patients with purulent meningitis at a comparably low dose.
authors.affiliation: The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Siming District, Xiamen, Fujian 361003, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Siming District, Xiamen, Fujian 361003, China.
authors.forename: Shengquan
authors.initials: S
authors.lastname: He
authors.affiliation: The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Siming District, Xiamen, Fujian 361003, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Siming District, Xiamen, Fujian 361003, China. Electronic address: 13959219339@126.com.
authors.forename: Congxia
authors.initials: C
authors.lastname: Lu
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D002681:China; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008578:Meninges / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; C511195:norvancomycin
keywords: CSF penetration; HPLC; Human; Meningitis; Norvancomycin; Pharmacokinetics