scholarly journals Pharmacokinetics of Amoxicillin in Maternal, Umbilical Cord, and Neonatal Sera

2009 ◽  
Vol 53 (4) ◽  
pp. 1574-1580 ◽  
Author(s):  
Anouk E. Muller ◽  
Paul M. Oostvogel ◽  
Joost DeJongh ◽  
Johan W. Mouton ◽  
Eric A. P. Steegers ◽  
...  

ABSTRACT The pharmacokinetics of amoxicillin were studied in umbilical cord and neonatal sera relative to maternal concentrations in prevention of neonatal group B streptococcus infection. The subjects were 44 pregnant women receiving amoxicillin as 1 or 2 g as an intravenous infusion. To measure the concentrations, blood samples were obtained from the mother, the arterial and venous umbilical cord, and the neonate. The pharmacokinetics were characterized by a five-compartment model by using nonlinear mixed-effects (population) modeling. The population estimates for the clearance, central volume of distribution, and the two peripheral maternal volumes of distribution were 19.7 ± 0.99 liters/h, 6.40 ± 0.61 liters, and 5.88 ± 0.83 liters (mean ± standard error), respectively. The volume of distribution of the venous umbilical cord and the neonatal volume of distribution were 3.40 liters and 11.9 liters, respectively. The pharmacokinetic parameter estimates were used to simulate the concentration-time profiles in maternal, venous umbilical cord, and neonatal sera. The peak concentration in the venous umbilical cord serum was 18% of the maternal peak concentration. It was reached 3.3 min after the maternal peak concentration. The concentration-time profile in neonatal serum was determined by the profile in venous umbilical cord serum, which in turn depended on the profile in maternal serum. Furthermore, the simulated concentrations in maternal, venous umbilical cord, and neonatal sera exceeded the MIC for group B streptococcus for more than 90% of the 4-h dosing interval. In a first approximation, the 2-g infusion to the mother appears to be adequate for the prevention of group B streptococcal disease. However, to investigate the efficacy of the prophylaxis, further studies of the interindividual variability in pharmacokinetics are indicated.

PEDIATRICS ◽  
1969 ◽  
Vol 44 (1) ◽  
pp. 49-57 ◽  
Author(s):  
John H. Dossett ◽  
Ralph C. Williams ◽  
Paul G. Quie

The bactericidal capacity of newborn infants' whole blood for E. coli was deficient compared to the mothers, and attempts were made to identify cellular or humoral factors responsible for this deficiency. Separated polymorphonuclear leukocytes from newborn infants were found to be similar to polymorphs from mothers in capacity to engulf and kill E. coli and other bacteria so that cellular deficiency was not evident. Comparison of the serum opsonic capacity of newborn infants' and mothers' sera revealed deficient opsonic capacity for E. coli in newborn sera. The mean opsonic titer for E. coli was 46.7 in mothers and 4.3 in neonates. Serum opsonic titers for Staph. aureus and group B streptococcus were similar. The opsonic capacity for all bacterial species was decreased when the sera were heated or decomplemented with immune complexes indicating the phagocytosis amplifying role of complement. The newborn-maternal difference in opsonic capacity for E. coli was presumably a result of deficient 19S antibodies, the primary opsonic antibodies for this organism. Maternal 19S serum fractions alone, however, showed no opsonic capacity for E. coli. Addition of a complement source (newborn serum absorbed with E. coli) revealed the opsonic capacity of these 19S maternal serum fractions for E. coli. Antibodies in 19S serum fractions therefore are efficient opsonins for E. coli; however, complement is necessary to demonstrate their opsonic potential.


2020 ◽  
Vol 19 (5) ◽  
pp. 29-35
Author(s):  
L.V. Renge ◽  
◽  
E.Yu. Grigoryeva ◽  
V.N. Zorina ◽  
A.E. Vlasenko ◽  
...  

Objective. To identify prognostic markers of intrauterine infection (IUI) of the fetus and newborn in maternal serum, amniotic fluid, and umbilical cord serum in case of preterm birth. Patients and methods. We examined 93 pregnant women who had preterm birth (PB) from 24 to 33 weeks of gestation. Thirtyfive women delivered babies without any signs of IUI, while 30 women had newborns with mild IUI (conjunctivitis, lymphadenitis, pyoderma) and 28 women had newborns with severe IUI (early neonatal sepsis, advanced herpesvirus infection, chlamydiosis, candidiasis, pneumonia, and meningitis). We measured the levels of alpha 2-macroglobulin (α2-MG) in maternal serum (MS), umbilical cord serum (UCS) using rocket immunoelectrophoresis and in amniotic fluid (AF) using enzyme-linked immunosorbent assay (ELISA). The level of lactoferrin (LF) was assessed using ELISA. MS and UCS levels of albumin (ALB) were measured using biochemical methods, while AF level ALB was evaluated using rocket immunoelectrophoresis. Statistical analysis was performed using logistic regression. Results. We found no association between the concentration of LF in all biological fluids and the condition of newborns. Levels of ALB in MS and UCS also demonstrated no correlation with the condition of newborns. AF ALB in women who delivered babies with IUI (any grade of severity) was significantly higher than that in women who delivered babies without IUI. Women who delivered babies with severe IUI demonstrated the lowest concentration of α2-MG in their serum, whereas women who delivered babies with mild IUI had the highest α2-MG concentration. The AF α2-MG level was 10 to 20 times higher in women who had babies with IUI (any grade of severity) compared to those who had babies without IUI. Conclusion. Low α2-MG level in MS (<2.2 g/L) along with elevated α2-MG level in AF (≥6.0 mg/L) in 86–89% of PB cases indicated generalized fetal IUI and required urgent delivery without prolongation of pregnancy. Key words: albumin, alpha-2-macroglobulin, intrauterine infection, lactoferrin. premature birth


1973 ◽  
Vol 19 (6) ◽  
pp. 602-607 ◽  
Author(s):  
Russell J Moser ◽  
Dorothy R Hollingsworth

Abstract A method is described for measurement of human chorionic somatomammotropin (HCS) by use of a double-antibody technique, for concentrations ranging from 2 ng/ml to 20 µg/ml. The cross-reactive characteristics of rabbit anti-human HCS serum No. CT 3399 from NIAMD are explored. A dilution plan is presented utilizing a standard curve from 0.75 to 80 ng/ml. Concentrations (mean and ranges) for HCS in maternal serum (evaluated every four weeks during pregnancy), umbilical cord serum, serum from babies, amniotic fluid, and urine are given.


2012 ◽  
Vol 15 (2) ◽  
pp. 265 ◽  
Author(s):  
Peng Zou ◽  
Nan Zheng ◽  
Yanke Yu ◽  
Shanghai Yu ◽  
Wei Sun ◽  
...  

Purpose. The two purposes of this study were evaluating preclinical pharmacokinetics of MI-219 and predicting clearance (CL) and volume of distribution at steady-state (Vdss) of MI-219 in humans. Methods. Pharmacokinetic studies were conducted on mice, rats, dogs, and monkeys. Human CL of MI-219 was predicted using allometric scaling (SA), multi-exponential allometric scaling (ME), rule of exponents (RoE), single species scaling, two-term power equation (TTPE), physiologically based in vitro-in vivo extrapolation (IVIVE), and fu corrected intercept method (FCIM). In vitro assays were conducted to determine in vitro intrinsic CL, protein binding, and blood-plasma partition coefficients. To estimate half-life of MI-219, plasma concentration–time profile in humans was predicted using kallynochron and apolysichron time transformation (Dedrick plots) and normalization with MRT and Vdss (Wajima’s method). In addition, simultaneous interspecies scaling of CL, Vdss and concentration–time profile were performed by using Nonlinear Mixed Effects Modeling (NONMEM). Results. Preclinical studies showed that the elimination of MI-219 was mainly through metabolism. The validation using observed monkey CL and Vdss showed that MA, IVIVE and Oie-Tozer methods were accurately than the other methods. Human CL of MI-219 predicted by ME and IVIVE was between 0.237-0.342 L*h-1*kg-1. Human Vdss predicted by Oie-Tozer method and allometric scaling of unbound volume of distribution of tissues (VT/fuT) method was between 0.93-1.40 L*kg-1. Superimposition of rat, monkey and dog data was observed in Dedrick plots and Wajima’s transformations. Conclusions. The predicted human pharmacokinetics is useful for the design of first-in-human study. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


2013 ◽  
Vol 99 (2) ◽  
pp. 168-173 ◽  
Author(s):  
Lei Sun ◽  
Zhen Jin ◽  
Weiping Teng ◽  
Xinshu Chi ◽  
Yanan Zhang ◽  
...  

2021 ◽  
Vol 26 ◽  
pp. 2515690X2110110
Author(s):  
Snehasis Biswas ◽  
Mukesh Chawda ◽  
Kapil Thakur ◽  
Ramacharya Gudi ◽  
Jayesh Bellare

Suvarna Bhasma (SB) is a gold particle-based medicine that is used in Ayurved to treat tuberculosis, arthritis and nervous diseases. Traditionally, the Ayurved preparation processes of SB do exist, but they are all long, tedious and involve several steps. Due to this, there is a possibility of bypassing the necessary Ayurved processes or non-adherence to all steps or use of synthetic gold particles. Our aim is to characterize 5 commercial SB preparations from 5 different manufacturers. A comparative physicochemical, pharmacokinetic (PK) and bioaccumulation study was carried out on all the 5 SB preparations. The general appearance such as color and texture of these 5 samples were different from each other. The size, shape and gold concentration (from 32-98 wt%) varied among all the 5 SBs. The accumulation of ionic gold in zebrafish and gold concentration profiles in rat blood were found to be significantly different for all the 5 SBs. Non-compartmental PK model obtained from the concentration-time profile showed significant differences in various PK parameters such as peak concentration (Cmax), half-life (t1/2) and terminal elimination slope (λz) for all the 5 SB preparations. SB-B showed the highest Cmax (8.55 μg/L), whereas SB-D showed the lowest Cmax (4.66 μg/L). The dissolution of ionic gold from SBs in zebrafish tissue after the oral dose had a 5.5-fold difference between the highest and lowest ionic gold concentrations. All the 5 samples showed distinct physicochemical and biological properties. Based on characteristic microscopic morphology, it was found that 2 preparations among them were suspected of being manufactured by non-adherence to the mentioned Ayurved references.


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