Penetration of potassium clavulanate/ticarcillin sodium into cerebrospinal fluid in neurosurgical patients

Abstract

Concentrations of potassium clavulanate (CVA) and ticarcillin sodium (TIPC) in the plasma and cerebrospinal fluid (CSF) of patients after neurosurgical intervention were determined at various times after a 1-hour drip infusion (3.2-g dose). Patients whose blood-brain barriers were supposed to be maintained in almost a normal condition were selected. CSF was obtained through a catheter placed in the anterior horn of the lateral ventricle in all the patients. Maximum plasma levels (micrograms/ml) of 57.6 to 384.0 with an average of 169.7 (TIPC) and 0.41 to 26.2 with an average of 6.1 (CVA) were achieved at the termination of infusion. The maximum CSF levels (micrograms/ml) were 0.61 to 18.8 (TIPC) and 0.1 to 6.81 (CVA) with mean values of 4.5 and 1.2, respectively. Plasma half lives (T1/2) (minute) were 24 to 93 (TIPC) and 32 to 227 with mean values of 58 and 127, respectively. The mean values of the CSF half lives (minute) were 237 (TIPC) and 113 (CVA). The ratios (%) of CSF levels to plasma levels in maximum concentration (Cmax), AUC (area under concentration curve) and half life (T1/2) were calculated. Cmax ratios were 0.2 to 29.2 (TIPC) and 1.4 to 69.8 (CVA) with mean values of 4.4 and 22.8, respectively. AUC ratios were 0.3 to 23.5 (TIPC) and 1.1 to 70.2 (CVA) with mean values of 4.3 and 22.4, respectively. T1/2 ratios were 1.3 to 18 (TIPC) and 1.1 to 4.3 (CVA) with mean values of 5.5 and 2.3, respectively. These values indicate that CVA/TIPC may be classified into a group of antibiotics with good penetration into the CSF.