Simultaneous quantification of cefuroxime and clindamycin in human lumbar anulus fibrosus, nucleus pulposus and serum via UPLC-MS/MS.

BACKGROUND: This study aimed to develop a sensitive, accurate method for simultaneously quantifying cefuroxime and clindamycin in human serum, lumbar anulus fibrosus and nucleus pulposus. METHODS: Cefuroxime and clindamycin were quantified using ultra high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in multiple-reaction-monitoring mode on a triple-quadrupole AB Qtrap 5500 system in positive ion mode. Internal standards were D3-cefuroxime and D3,13C-clindamycin. Samples were pretreated by precipitating total protein. RESULTS: The method showed high sensitivity and good linearity over broad calibration ranges from 100 to 100 000 ng/mL for cefuroxime and 10 to 10 000 ng/mL for clindamycin in serum, and from 10 to 10 000 ng/mL for cefuroxime and 1 to 1 000 ng/mL for clindamycin in lumbar nucleus pulposus. In all sample types, correlation coefficients were greater than 0.99, intra- and inter-day precision (relative standard deviation) was less than 15%, and accuracy (relative error) was within 14% for both analytes. This method was effective at quantifying penetration of cefuroxime and clindamycin in patients undergoing oblique lumbar interbody fusion surgery. CONCLUSIONS: A very sensitive, specific method for simultaneous detection of cefuroxime and clindamycin has been developed for human lumbar anulus fibrosus, nucleus pulposus and serum samples.

Pregnancy-related pharmacokinetics and antimicrobial prophylaxis during fetal surgery, cefazolin and clindamycin as examples.

Antimicrobial prophylaxis during surgery aims to prevent post-operative site infections. For fetal surgery, this includes the fetal and amniotic compartments. Both are deep compartments as drug equilibrium with maternal blood is achieved relatively late. Despite prophylaxis, chorio-amnionitis or endometritis following ex utero intrapartum treatment or fetoscopy occur in 4.13% and 1.45% respectively of the interventions. This review summarizes the observations on two commonly administered antimicrobials (cefazolin, clindamycin) for surgical prophylaxis during pregnancy, with emphasis on the deep compartments. For both compounds, antimicrobial exposure is on target when we consider the maternal and fetal plasma compartment. In contrast, amniotic fluid concentrations-time profiles display a delayed and much more blunted pattern, behaving as deep compartment. For cefazolin, there are data that document further dilution in the setting of polyhydramnios. Along this deep compartment concept, there is some accumulation during repeated administration, modeled for cefazolin and observed for clindamycin. The relative underexposure to antimicrobials in amniotic fluid may be reflected in the pattern of maternal-fetal complications after fetal surgery, and suggest that antimicrobial prophylaxis practices for fetal surgery should be reconsidered. Further studies should be designed by a multidisciplinary team (fetal surgeons, clinical pharmacologists and microbiologists) to facilitate efficient evaluation of antimicrobial prophylaxis.

Determination of free clindamycin, flucloxacillin or tedizolid in plasma: Pay attention to physiological conditions when using ultrafiltration.

Pharmacokinetic/pharmacodynamic indices of anti-infective drugs should be referenced to free drug concentrations. In the present study, clindamycin, flucloxacillin and tedizolid have been determined in human plasma by HPLC-UV. The drugs were separated isocratically within 3-6 min on a C18 column using mixtures of phosphate buffer-acetonitrile of pH 7.1-7.2. Sample treatment for the determination of total drug concentrations in plasma included extraction/back-extraction (clindamycin) or protein precipitation (flucloxacillin, tedizolid). The free drug concentrations were determined after ultrafiltration. An ultrafiltration device with a membrane consisting of regenerated cellulose proved to be suitable for all drugs. Maintaining a physiological pH was crucial for clindamycin, whereas maintaining body temperature was essential for tedizolid. The methods were applied to the analysis of total and free drug concentrations in clinical samples and were sufficiently sensitive for pharmacokinetic studies and therapeutic drug monitoring.

Sensitive analytical method to quantify clindamycin in plasma and microdialysate samples: Application in a preclinical pharmacokinetic study.

Clindamycin is widely used in antimicrobial prophylaxis to prevent surgical site infections. Adequate subcutaneous free tissue concentrations should reach therapeutic levels, which have to be maintained throughout the surgical procedure for antibiotic prophylaxis to be efficient. A method was developed and validated using high performance liquid chromatography coupled to a mass spectrometry to determine clindamycin concentrations in two biological matrices: plasma, for drug monitoring, and subcutaneous microdialysate, to determine free concentrations at the incision site. Gradient separation of clindamycin was carried out using a reverse phase C18 column eluted with a mixture of mobile phases (1% formic acid in water and 1% formic acid in acetonitrile). The monitored transitions were m/z 425.3 > 377.3 for clindamycin, and m/z 407 > 359 for lincomycin, used as the internal standard for plasma samples. Linearity was reached in the 0.5-100 µg/mL range for plasma and 25-1000 ng/mL for microdialysate samples. The method was selective, precise, and accurate, and was successfully employed in a preliminary pharmacokinetics study to investigate plasma and subcutaneous clindamycin penetration, determined by microdialysis, after intravenous administration of a 50 mg/kg dose to Wistar rats.

Pharmacokinetics of intravenous clindamycin phosphate in captive Bennett's wallabies (Macropus rufogriseus).

This study was designed to investigate the pharmacokinetics of clindamycin, a lincosamide antibiotic, in Bennett's wallabies. The pharmacokinetic properties of a single intravenous (IV) dose of clindamycin were determined in six wallabies. A single 20-min IV infusion of 20 mg/kg of clindamycin was administered, followed by blood collection prior to, and up to 12 hr after clindamycin administration. Plasma clindamycin concentrations were determined by high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Pharmacokinetic variables were calculated using a two-compartment model with first order elimination which best fit the data. The mean volume of distribution at steady-state, distribution half-life, and elimination half-life were 898.25 ml/kg, 0.16 hr, 1.79 hr, respectively. No adverse effects were noted after IV administration.

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

Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool used to characterize maturational changes in drug disposition to inform dosing across childhood; however, its use is limited in pediatric drug development. Access to pediatric pharmacokinetic data is a barrier to widespread application of this model, which impedes its development and optimization. To support the development of a pediatric PBPK model, we sought to leverage opportunistically-collected plasma concentrations of the commonly used antibiotic clindamycin. The pediatric PBPK model was optimized following development of an adult PBPK model that adequately described literature data. We evaluated the predictability of the pediatric population PBPK model across four age groups and found that 63-93% of the observed data were captured within the 90% prediction interval of the model. We then used the pediatric PBPK model to optimize intravenous clindamycin dosing for a future prospective validation trial. The optimal dosing proposed by this model was 9 mg/kg/dose in children ≤5 months of age, 12 mg/kg/dose in children >5 months-6 years of age, and 10 mg/kg/dose in children 6-18 years of age, all administered every 8 h. The simulated exposures achieved with the dosing regimen proposed were comparable with adult plasma and tissue exposures for the treatment of community-acquired methicillin-resistant Staphylococcus aureus infections. Our model demonstrated the feasibility of using opportunistic pediatric data to develop pediatric PBPK models, extending the reach of this powerful modeling tool and potentially transforming the pediatric drug development field.

Pharmacokinetics of Clindamycin in Obese and Nonobese Children.

Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size. The final model included TBW and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (liters/hour) = 13.8 × (TBW/70)0.75 × [PMA2.83/(39.52.83+PMA2.83)]; volume of distribution (V) was associated with TBW, albumin (ALB), and alpha-1 acid glycoprotein (AAG): V (liters) = 63.6 × (TBW/70) × (ALB/3.3)-0.83 × (AAG/2.4)-0.25 After accounting for differences in TBW, obesity status did not explain additional interindividual variability in model parameters. Our findings support TBW-based dosing for obese and nonobese children.

Evaluation of Different Oral Formulations of Clindamycin Extended Release in Dogs.

The purpose of this study was to evaluate the pharmacokinetics of extended-release formulations (ERFs) of clindamycin with polymeric-based matrices. In a crossover study, 21 healthy adult dogs were randomly assigned (in groups of 7) to receive a single oral dose (20 mg/kg) of clindamycin without excipients (control) or an extended-release formulation containing clindamycin+Hydroxypropyl methylcellulose (HPMC)+poloxamer at a ratio of 1 : 0.04 : 0.5 (ERF1) or containing clindamycin+HPMC+acrylic acid polymer (AAP) at the same proportions (ERF2). Serum clindamycin concentrations were determined for pharmacokinetic analysis prior to and at several time intervals after each treatment. Following the oral administration in study dogs, each ERF resulted in therapeutic serum clindamycin concentrations for 60 h, whereas the control treatment resulted in therapeutic serum clindamycin concentrations for only 12 h. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different from those of the control treatment. These results indicate that both ERFs composed of a polymeric matrix containing clindamycin, HPMC, and AAP or poloxamer demonstrated an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and provided a longer release period than clindamycin alone following oral administration in dogs. Given that the minimum effective serum concentration of clindamycin is 0.3 µg/mL, a dose interval of 60 h could be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in infections in dogs. The treatment of dogs with either ERF may provide several benefits over treatment with clindamycin alone.

Transplacental passage of clindamycin from mother to neonate.

OBJECTIVE: To evaluate maternal and neonatal cord blood levels at delivery in patients receiving 900 mg of clindamycin intravenous (IV) every 8 h. STUDY DESIGN: Prospective study consented every mother that entered labor with a positive group B streptococcal culture, a high-risk penicillin allergy, and sensitivity to clindamycin and erythromycin. Maternal and cord blood clindamycin levels were obtained at delivery. Time from last dose completion to delivery, number of doses administered and body mass index (BMI) were assessed. RESULTS: Twenty-three patients were consented. All maternal clindamycin values were therapeutic and 22 (96%) of the 23 cord blood samples were therapeutic. The mean maternal level was of 4.46 µg ml-1 (range of 0.7 to 8.4 µg ml-1). The mean cord blood level was 3.35 µg ml-1 (range of <0.5 to 6.4 µg ml-1). CONCLUSION: These data show that the current dosing recommendation of 900 mg of clindamycin IV every 8 h produces therapeutic maternal and cord blood levels.

In vitro and in vivo Evaluation of Synergism between Anti-Tubercular Spectinamides and Non-Classical Tuberculosis Antibiotics.

Spectinamides are new semi-synthetic spectinomycin derivatives with potent anti-tubercular activity. The reported synergism of the precursor spectinomycin with other antibiotics prompted us to examine whether spectinamides sensitize M. tuberculosis to other antibiotics not traditionally used in the treatment of tuberculosis to potentially expand therapeutic options for MDR/XDR Tuberculosis. Whole cell synergy checkerboard screens were performed using the laboratory strain M. tuberculosis H37Rv, lead spectinamide 1599, and a broad panel of 27 antibiotics. In vitro, 1599 synergized with 11 drugs from 6 antibiotic classes. The observed synergy was tested against clinical isolates confirming synergy with Clarithromycin, Doxycycline and Clindamycin, combinations of which were taken forward for in vivo efficacy determination. Co-administration of 1599 and clarithromycin provided additional bacterial killing in a mouse model of acute tuberculosis infection, but not in a chronic infection model. Further studies indicated that mismatched drug exposure profiles likely permitted induction of phenotypic clarithromycin resistance and subsequent loss of synergism. These studies highlight the importance of validating in vitro synergism and the challenge of matching drug exposures to obtain a synergistic outcome in vivo. Results from this study indicate that a 1599 clarithromycin combination is potentially viable, providing the drug exposures can be carefully monitored.

Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.

PURPOSE: Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome. METHODS: An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L. RESULTS: Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin. CONCLUSIONS: This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

Antibiotic penetration into rabbit nucleus pulposus with discitis.

OBJECTIVE: To assess the penetration into nucleus pulposus (NP) of cephazolin and clindamycin in a discitis model. MATERIALS AND METHODS: Twenty New Zealand white rabbits were inoculated with 103 Staphylococcus aureus at lumbar disc space. The rabbits with discitis confirmed by MRI 10 days after inoculation were divided into two groups. One was given cephazolin by intravenous (IV) at 80 mg/kg/day at 1.5 h interval for 5 half-lives; the other was given clindamycin by IV at 30 mg/kg/day at 2.5-h interval for 5 half-lives. Thirty minutes after completion of the last dose, NP and serum were sent to measure antibiotic concentration. RESULTS: Two rabbits died during inoculation. After 10 days, 18 rabbits were confirmed discitis in the inoculated levels. The cephazolin and clindamycin can diffuse throughout the infected, sham-infected and normal NP. The serum concentration of cephazolin and clindamycin was 251.3 ± 40.5 and 21.6 ± 4.71 mg/l, respectively. The cephazolin concentration in infected NP (1.93 ± 0.84 mg/l) was higher than that in sham-infected (1.73 ± 0.61 mg/l) and normal NP (1.68 ± 0.65 mg/l), but the difference showed no statistically significant (P > 0.05). The cephazolin penetration into NP averaged 0.68-0.77 % of serum level. The clindamycin concentration in infected NP (4.32 ± 1.54 mg/l) was higher than that in sham-infected NP (2.63 ± 1.26 mg/l) and normal NP (2.59 ± 1.01 mg/l) (P < 0.05). The penetration into NP averaged 11.9-20 % of serum level. There was no significance difference between sham-infected and normal NP in clindamycin and cephazolin concentration (P > 0.05). CONCLUSIONS: This study demonstrates cephazolin and clindamycin can penetrate the infected and normal NP. The antibiotics charge influences the delivery. Furthermore, infection condition selectively promotes antibiotic distribution within NP.

Elution of antimicrobials from a cross-linked dextran gel: In vivo quantification.

REASONS FOR PERFORMING STUDY: Use of a novel, biodegradable, antimicrobial-impregnated gel provides an alternative method of local treatment of infections in horses. OBJECTIVES: To determine in vivo elution of antimicrobial medications from antimicrobial-impregnated cross-linked dextran gel and to evaluate the effect on wound healing when implanted subcutaneously in horses. METHODS: Amikacin-, vancomycin- or amikacin/clindamycin-impregnated gel was placed subcutaneously in 11 horses' necks, using 6 replicates with a 3 month washout between experiments. Capillary ultrafiltration probes for collection of interstitial fluid were placed 0 cm and 1.5 cm from the gel-filled incisions. Samples were collected at 0, 4, 8 and 12 h, and on Days 1-10. Blood was collected on Days 0, 1 and 7. Amikacin and vancomycin samples were analysed via fluorescence polarisation immunoassay, and clindamycin samples via high-performance liquid chromatography. Histology of biopsy samples was performed at the completion of the study. Differences in mean histomorphological scores between groups were assessed using Wilcoxon's signed ranks test. RESULTS: Maximum antimicrobial concentrations were detected at 4 h (amikacin), and 8 h (vancomycin, and amikacin and clindamycin from the combination gel). Mean ± s.d. peak concentrations for amikacin, vancomycin, amikacin (amikacin/clindamycin) and clindamycin were 6133 ± 1461, 7286 ± 2769, 3948 ± 317 and 985 ± 960, respectively. Median number of days for which antimicrobial concentration remained above minimum inhibitory concentration for target microorganisms at implantation was ≥10 days for vancomycin, 9 days (± 1) for amikacin and 8 days (± 1) for clindamycin. Mean plasma amikacin and vancomycin concentrations were lower than detectable limits; mean serum clindamycin concentrations were 0.52 µg/ml and 0.63 µg/ml at 24 h and 7 days, respectively. There were no significant differences in histomorphological scores between treatment and control incisions (P≥0.22). CONCLUSIONS AND POTENTIAL RELEVANCE: Cross-linked dextran gel is a safe, effective alternative local antimicrobial delivery method.

Pharmacokinetics of clindamycin in the plasma and dialysate after intraperitoneal administration of clindamycin phosphoester to patients on continuous ambulatory peritoneal dialysis: an open-label, prospective, single-dose, two-institution study.

We evaluated the pharmacokinetics of clindamycin and the dose of clindamycin phosphate necessary to treat peritonitis after intraperitoneal administration of clindamycin phosphate to patients on continuous ambulatory peritoneal dialysis (CAPD). This was an open-label, prospective, single-dose study conducted at the two levels of institutional clinical care in South Korea. Twelve patients (six men and six women; all older than 25 years), mean CAPD duration of 38.2 months with various origins without peritonitis, received 600 mg clindamycin phosphate mixed with only the first 2-L dialysate (1.5% dextrose). The 1.5%, 1.5%, 2.5% and 1.5% dextrose dialysates were serially exchanged every 6 hr. If patients were non-anuric, 24-hr urine samples were also collected. Clindamycin phosphate was incompletely activated to clindamycin in the dialysate. The clindamycin concentration in the dialysate was greater than the effective concentration (5 µg/mL) at 6.87 µg/mL up to 6 hr. So, 600 mg clindamycin phosphate per every 6 hr dialysate is effective for treatment of peritonitis. It has been reported that the clindamycin concentrations in the dialysate may be higher in CAPD patients with peritonitis. Thus, we can expect that intraperitoneal administration of <600 mg clindamycin phosphate per every 6 hr dialysate could be maintained over 5 µg/mL in patients with peritonitis. The transfer of clindamycin was unidirectional from the dialysate to the plasma.

Serum pharmacokinetics of clindamycin hydrochloride in normal dogs when administered at two dosage regimens.

The aim of this cross-over study was to compare clindamycin pharmacokinetics in the serum of clinically normal dogs when administered orally at two dosage regimens (5.5 mg/kg, twice daily, and 11 mg/kg, once daily), separated by a 1 week wash-out period. Serum samples were obtained from six clinically normal laboratory beagles before, 3, 6, 9 and 12 h after the first and fifth dose of clindamycin at 5.5 mg/kg, twice daily, and before, 3, 6, 9, 12, 18 and 24 h after the first and third dose at 11 mg/kg, once daily. Serum clindamycin concentrations were determined by reverse-phase liquid chromatography coupled with mass spectrometry. Results were analysed using Student's paired t-test, at a 5% level of significance. Values of pharmacokinetic parameters that differed significantly between the two dosage regimens included the following: maximal concentration and area under the concentration-time curve were higher at 11 mg/kg, once daily, than at 5.5 mg/kg, twice daily; and, more importantly, the ratio of AUC(0-24) to the minimal inhibitory concentration (MIC) value of 0.5 µg/mL for a 24 h period (AUC(0-24)/MIC) was higher when clindamycin was administered at 11 than at 5.5 mg/kg, at least during the first day of drug administration. Therefore, a better pharmacokinetic profile may be expected when clindamycin is administered at 11 mg/kg, once daily, for the treatment of canine pyoderma caused by Staphylococcus pseudintermedius.

Pharmacokinetics of clindamycin administered orally to pigeons.

To determine the plasma concentration of clindamycin in pigeons after oral administration, 12 rock pigeons (Columba livia) were used in a 2-phase study. In the first phase, 8 pigeons received clindamycin by gavage at 100 mg/kg as a single dose. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 3, 4, and 6 hours, and the plasma was separated, frozen, and subsequently analyzed by liquid chromatography-mass spectrometry for clindamycin and its active metabolites, N-demethylclindamycin (NCLD) and clindamycin sulfoxide. Clindamycin was rapidly absorbed with plasma concentrations peaking at 0.5 hours at 1.43 microg/mL. The terminal half-life (t(1/2)) was 1.25 hours, and the mean residence time was 2.49 hours. N-demethylclindamycin was detected in 7 of 8 birds (88%), whereas clindamycin sulfoxide was not found in any samples. In phase 2, clindamycin was administered to 3 birds by gavage at 100 mg/ kg q6h for 5 doses. Mean peak plasma concentrations were 2.46 and 0.64 microg/mL, with trough concentrations of 0.11 and 0.44 microg/mL for clindamycin and NCLD, respectively. No adverse effects were observed in any birds. Based on an additive antimicrobial effect of NCLD with clindamycin, an oral dosage of 100 mg/kg q6h in pigeons should reach effective plasma concentrations against common susceptible pathogens. If dose proportionality exists, lower doses and longer intervals likely produce subtherapeutic concentrations to treat systemic infections. How well birds would tolerate an extended oral dose regimen, how frequently birds fail to produce the active metabolite critical for an additive effect, and the application of these results to other avian species require further study.

Artesunate-clindamycin multi-kinetics and site-specific oral delivery system for antimalaric combination products.

The aim of this work was to study a multi-kinetics and site-specific oral antimalaria drug delivery system (MKS_DDS), containing artesunate and clindamycin, based on the Dome Matrix module assembly technology. The MKS_DDS assembled system comprises of four modules, i.e., two controlled release (CR) modules for delivery of 160 mg of clindamycin phosphate, one immediate release module containing 50 mg of artesunate and one immediate release module containing 80 mg of clindamycin phosphate. These modules have been assembled in stacked and void configurations. The void configuration is able to float and showed gastro-retentive behavior. The MKS_DDS was investigated for its mechanical characteristics, system behavior during release, drug release rate and mechanism. A bioavailability study (dogs) showed that the clindamycin plasma curve of the MKS_DDS system exhibited a quasi constant release rate, up to 8 h. The MKS_DDS system containing clindamycin and artesunate allows the use of one tablet containing one immediate release dose of artesunate and of clindamycin and a portion of clindamycin released over a prolonged time, by exploiting the gastro-retentive properties of a floating system.

Pharmacokinetics of clindamycin in pregnant women in the peripartum period.

The study presented here was performed to determine the pharmacokinetics of intravenously administered clindamycin in pregnant women. Seven pregnant women treated with clindamycin were recruited. Maternal blood and arterial and venous umbilical cord blood samples were obtained. Maternal clindamycin concentrations were analyzed by nonlinear mixed-effects modeling with the NONMEM program. The data were best described by a linear three-compartment model. The clearance and the volume of distribution at steady state were 10.0 liters/h and 6.32 x 10(3) liters, respectively. Monte Carlo simulations were performed to determine the area under the concentration curve (AUC) for the free (unbound) drug (f) in maternal serum for 24 h divided by the MIC (fAUC(0-24)/MIC). At a MIC of 0.5 mg/liter, which is the EUCAST breakpoint, the attainment at the lower 95% confidence interval (CI) was 24.6 if the level of protein binding was 65%, and this value concurred well with the target value of 27. However, for higher degrees of protein binding, as has been described in the literature, the attainment was lower, down to 10.2 for a protein binding level of 85% (lower 95% CI). The concentrations in umbilical cord blood were lower than those in maternal blood. The concentration-time profiles in maternal serum indicate that the level of exposure to clindamycin may be too low in these patients. Together with the lower concentrations in umbilical cord blood, this finding suggests that the current dosing regimen may not be adequate to protect all neonates from group B streptococcal disease.