scholarly journals Valproic Acid Concentrations in Mothers, Colostrum and Breastfed Infants during the Early Postpartum Period: Comparison with Concentrations Determined during Delivery and in the Mature Milk Period

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2074
Author(s):  
Ivana Kacirova ◽  
Milan Grundmann ◽  
Hana Brozmanova
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Lower Limit ◽  
Concentration Ratio ◽  
Maternal Serum ◽  
Serum Concentrations ◽  
Limit Of Quantification ◽  
Mature Milk ◽  
Breastfed Infants ◽  
Routine Monitoring

To obtain information on the transport of valproic acid from mothers to colostrum and breastfed infants, in this cohort study, valproic acid concentrations in maternal serum (90 subjects), colostrum and the serum of breastfed infants were analyzed in years 1993–2018, between the 2nd and 5th postnatal days. Valproic acid concentrations ranged from 4.3 to 66.5 mg/L (mean 31.2 ± 13.6 mg/L) in maternal serum, from 0.5 to 5.9 mg/L (mean 1.1 ± 1.2 mg/L) in milk, and from 0.5 to 42.9 mg/L (mean 15.4 ± 9.4 mg/L) in infant serum. The milk/maternal serum concentration ratio ranged from 0.01 to 0.22 (mean 0.04 ± 0.04), and the infant/maternal serum concentration ratio ranged from 0.01 to 1.61 (mean 0.51 ± 0.28). A significant correlation was found between serum concentrations of breastfed infants and milk concentrations, maternal serum concentrations, maternal daily dose, and dose related to maternal body weight. Valproic acid concentrations in milk and infant serum did not reach the lower limit of the reference range used for the general epileptic population, and three-quarters of the concentrations in milk were lower than the lower limit of quantification. Routine monitoring of serum concentrations of breastfed infants is not necessary. If signs of potential adverse reactions are noted, serum concentrations of the infants should be measured.

scholarly journals Umbilical Cord, Maternal Milk and Breastfed Infant Levetiracetam Concentrations Monitoring at Delivery and during Early Postpartum Period

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 398
Author(s):  
Ivana Kacirova ◽  
Milan Grundmann ◽  
Hana Brozmanova
Keyword(s):  
Serum Concentration ◽  
Umbilical Cord ◽  
Concentration Ratio ◽  
Combined Treatment ◽  
Maternal Serum ◽  
Breastfed Infant ◽  
Serum Concentrations ◽  
Mature Milk ◽  
Cord Serum ◽  
The Mean

(1) To obtain objective information about levetiracetam transplacental passage and its transport into colostrum, mature milk, and breastfed infants, we analyzed data from women treated for epilepsy between October 2006 and January 2021; (2) in this cohort study, maternal, umbilical cord, milk, and infant serum concentrations were measured at delivery, 2–4 days postpartum (colostrum) and 7–31 days postpartum (mature milk). Paired umbilical cord serum, maternal serum, breastfed infant serum, and milk concentrations were used to assess the ratios of umbilical cord/maternal serum, milk/maternal serum, and infant/maternal serum concentrations. The influence of combined treatment with enzyme-inducing antiseizure medication carbamazepine was assessed; (3) the umbilical cord/maternal serum concentration ratio ranged between 0.75 and 1.78 (mean 1.10 ± 0.33), paired maternal and umbilical cord serum concentrations were not significantly different, and a highly significant correlation was found between both concentrations. The mean milk/maternal serum concentration ratio was 1.14 ± 0.27 (2–4 days postpartum) and 1.04 ± 0.24 (7–31 days postpartum) while the mean infant/maternal serum concentration ratio was markedly lower (0.19 ± 0.13 and 0.14 ± 0.05, respectively); (4) levetiracetam was found in the umbilical cord at a concentration similar to those in maternal serum. All of the breastfed infant serum concentrations were below the reference range used for the general epileptic population.

Elevated Free Fractions of Valproic Acid in a Heart Transplant Patient with Hypoalbuminemia

2000 ◽  
Vol 34 (2) ◽  
pp. 183-187 ◽  
Author(s):  
Jeffrey A Haroldson ◽  
Linda E Kramer ◽  
Denise L Wolff ◽  
Kathleen D Lake
Keyword(s):  
Valproic Acid ◽  
Adverse Effects ◽  
Serum Concentration ◽  
Transplant Patient ◽  
Total Serum ◽  
Heart Transplant Patient ◽  
Serum Concentrations ◽  
Case Summary ◽  
Related Adverse Effect ◽  
Drug Concentrations

OBJECTIVE: To report a case demonstrating the importance of monitoring unbound valproic acid (VPA) serum concentrations in a patient with hypoalbuminemia. CASE SUMMARY: A 53-year-old white woman status–post heart transplantation was admitted to the hospital for declining cardiac function, possible rejection, and increased lethargy requiring intubation. An extensive workup of the patient's profound lethargy was initiated, including an evaluation of her VPA regimen. Initially, VPA dosages were adjusted based on the total serum concentration of VPA. Hypoalbuminemia compounded with increased lethargy prompted the measurement of unbound serum concentrations of VPA. The VPA dosage was then adjusted based on the unbound rather than the total VPA serum concentration; the patient eventually improved and was discharged from the hospital. DISCUSSION: Lethargy is a concentration-related adverse effect of VPA. The nonlinear pharmacokinetic and protein saturation characteristics of VPA may result in nonproportional elevations in unbound drug, and subsequent increases in adverse effects, when dosage adjustments are based solely on measurement of total VPA serum concentrations in patients with hypoalbuminemia. CONCLUSIONS: This case report suggests that appropriate monitoring of unbound drug concentrations of VPA may prevent unrecognized concentration-related adverse effects. Awareness of the pharmacokinetic relationship and adverse effects of VPA will aid clinicians in identifying the etiology of symptoms.

scholarly journals Neonatal Feeding Trajectories in Mothers With Bipolar Disorder Taking Lithium: Pharmacokinetic Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Luisa Imaz ◽  
Klaus Langohr ◽  
Mercè Torra ◽  
Dolors Soy ◽  
Luisa García-Esteve ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Exclusive Breastfeeding ◽  
Lithium Concentration ◽  
Late Pregnancy ◽  
Maternal Serum ◽  
Pharmacokinetic Data ◽  
Serum Concentrations ◽  
Limit Of Quantification ◽  
Pregnancy And Postpartum ◽  
Exclusive Or

Purpose: Women who take lithium during pregnancy and continue after delivery may choose to breastfeed, formula feed, or mix these options. The aim of the study was to evaluate the neonatal lithium serum concentrations based on these three feeding trajectories.Methods: We followed 24 women with bipolar disorder treated with lithium monotherapy during late pregnancy and postpartum (8 per trajectory). Lithium serum concentrations were determined by an AVL 9180 electrolyte analyser with a 0.10 mEq/L detection limit and a 0.20 mEq/L limit of quantification (LoQ).Results: There was complete lithium placental passage at delivery, with a mean ratio of lithium concentration in the umbilical cord to maternal serum of 1.12 ± 0.17. The median times to LoQ were 6–8, 7–8, and 53–60 days for formula, mixed, and exclusive breastfeeding respectively. The generalized log-rank testing indicated that the median times to LoQ differ according to feeding trajectory (p = 0.037). According to the multivariate analysis-adjusted lithium serum concentrations at birth, times to LoQ are, on average, longer under exclusive breastfeeding (formula, p = 0.015; mixed, p = 0.012). No lithium accumulation was observed in infants under either exclusive or mixed breastfeeding. During the lactation follow-up, there was no acute growth or developmental delays in any neonate or infant. Indeed, lithium concentrations in the three trajectories declined in all cases. However, the time needed to reach the LoQ was much longer for those breastfeeding exclusively.Conclusions: In breastfeed infant no sustained accumulation of lithium and no adverse effects on development or growth were observed.

scholarly journals Dexamethasone serum concentrations after intravenous administration in horses during race training

2020 ◽  
pp. 1-10
Author(s):  
S. McClure ◽  
C. Fenger ◽  
K. Kersh ◽  
B. Brown ◽  
G. Maylin ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Intravenous Administration ◽  
Sodium Phosphate ◽  
Limit Of Detection ◽  
Serum Concentrations ◽  
Concentration Data ◽  
Limit Of Quantification ◽  
Inflammatory Conditions ◽  
Standard Deviation Range ◽  
The Usa

Dexamethasone (DXM) sodium phosphate is a widely used corticosteroid for inflammatory conditions in horses, regulated in racing jurisdictions in the USA by a 0.005 ng/ml serum/plasma threshold. This study seeks to describe serum concentrations of DXM at 48 and 72 h after intravenous administration of 20 mg DXM sodium phosphate over 1 to 5 days, and to identify a possible source of DXM overages. 74 horses (39 Thoroughbreds, 13 Standardbreds, 22 Quarter Horses) in active race training received 20 mg DXM sodium phosphate. Serum was collected before injection, at 48 and 72 h post last injection, and analysed by LC/MS-MS (limit of quantification (LOQ) = 2.5 pg/ml). No differences were identified by ANOVA (P≤0.05) for racing breeds, age, gender or the number of days of DXM sodium phosphate administration, so data were pooled for each time point. The DXM serum concentration at 48 h (mean ± standard deviation, range) was 2.18±1.56 pg/ml (<2.5 to 40 pg/ml). Summary statistics could not be derived for 72 h DXM serum concentration data owing to censored data, but ranged from <2.5 to 95.8 pg/ml. There was one extreme outlier (Tukey) at 48 h, and two extreme outliers at 72 h. A separate study was conducted using sedentary experimental horses to determine the likelihood that positive DXM samples could result from environmental transfer. Urine was collected from a mare 2 to 3 h post administration of 20 mg DXM. Hay with 100 ml of the DXM (17 ng/ml) containing urine was offered to each of six experimental horses and blood was collected at 0, 4, 8, 12, 16, 20 and 24 h. All six horses had plasma DXM concentration above the limit of detection and five of six had plasma DXM concentrations above the LOQ for at least one sample time.

Acute Seizures Due to a Probable Interaction between Valproic Acid and Meropenem

2005 ◽  
Vol 39 (3) ◽  
pp. 533-537 ◽  
Author(s):  
Francisco Javier Coves-Orts ◽  
Joaquín Borrás-Blasco ◽  
Andrés Navarro-Ruiz ◽  
Ana Murcia-López ◽  
Francisco Palacios-Ortega
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Epileptic Seizures ◽  
Clonic Seizure ◽  
Experimental Models ◽  
Tonic Clonic Seizure ◽  
Serum Concentrations ◽  
Intensive Care Unit Treatment ◽  
Acute Seizures ◽  
Probable Interaction

OBJECTIVE: To report a probable interaction between meropenem and valproic acid that resulted in the development of epileptic seizures. CASE SUMMARY: A 21-year-old woman presented to our emergency department because of a new-onset, generalized tonic—clonic seizure and was admitted to the intensive care unit. Treatment with valproic acid 1000 mg as a continuous intravenous infusion over 24 hours was initiated. On day 6, the serum concentration of valproic acid was 52.5 μg/mL. On day 13, treatment with intravenous meropenem 1 g 3 times daily was started. On day 15, when the patient was afebrile, numerous myoclonic episodes occurred involving her arms and face; the serum concentration of valproic acid at that time was 42 μg/mL. The valproic acid dose was increased to 2880 mg. Two days later, a generalized tonic—clonic seizure occurred despite the increased dosage, and the plasma concentration of valproic acid fell to 7 μg/mL. The valproic acid dose was increased the following day to 3600 mg; however, the serum concentrations remained <10 μg/mL. On day 19, based on the results of a blood culture and the suspicion of an interaction between meropenem and valproic acid, meropenem therapy was suspended. The serum concentration of valproic acid was 52.4 μg/mL on day 27. Three days later, the patient was asymptomatic and was discharged. DISCUSSION: Coadministration of valproic acid and other drugs that are metabolized by the hepatic cytochrome P450 isoenzyme system can lead to clinically relevant interactions by induction or inhibition of enzymes in shared metabolic pathways. In view of studies in experimental models, the interaction between carbapenem antibiotics and valproic acid is at least possible. Use of the Naranjo probability scale indicated a probable relationship between acute seizures and a meropenem—valproic acid interaction in this patient. CONCLUSIONS: This case report provides strong evidence for an interaction between valproic acid and meropenem. Clinicians should be aware of this potential interaction that may be associated with a serious adverse effect as the result of the decrease of the valproic acid serum concentrations.

scholarly journals Maternal Serum Concentrations of Selenium, Copper, and Zinc during Pregnancy Are Associated with Risk of Spontaneous Preterm Birth: A Case-Control Study from Malawi

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Grace Chiudzu ◽  
Augustine T. Choko ◽  
Alfred Maluwa ◽  
Sandra Huber ◽  
Jon Odland
Keyword(s):  
Preterm Birth ◽  
Serum Concentration ◽  
Case Control Study ◽  
Case Control ◽  
High Serum ◽  
Maternal Serum ◽  
Serum Concentrations ◽  
Spontaneous Preterm Birth ◽  
Copper And Zinc ◽  
Control Study

Preterm birth is delivery before 37 completed weeks. A study was conducted to evaluate the association of maternal serum concentrations of selenium, copper, and zinc and preterm birth. There were 181 women in this nested case-control study, 90/181 (49.7%) term and 91/181 (50.3%) preterm pregnant women. The overall mean serum concentration of selenium was 77.0, SD 19.4 μg/L; of copper was 2.50, SD 0.52 mg/L; and of zinc was 0.77, SD 0.20 mg/L with reference values of 47-142 μg/L, 0.76-1.59 mg/L, and 0.59-1.11 mg/L, respectively. For preterm birth, mean serum concentration for selenium was 79.7, SD 21.6 μg/L; for copper was 2.61, SD 0.57 mg/L; and for zinc was 0.81, SD 0.20 mg/L compared to that for term births: selenium (74.2; SD 16.5 μg/L; p=0.058), copper (2.39; SD 0.43 mg/L; p=0.004), and zinc (0.73; SD 0.19 mg/L; p=0.006), respectively. In an adjusted analysis, every unit increase in maternal selenium concentrations gave increased odds of being a case OR 1.01 (95% CI: 0.99; 1.03), p=0.234; copper OR 1.62 (95% CI: 0.80; 3.32), p=0.184; zinc OR 6.88 (95% CI: 1.25; 43.67), p=0.032. Results show that there was no deficiency of selenium and zinc and there were high serum concentrations of copper in pregnancy. Preterm birth was associated with higher maternal serum concentrations of copper and zinc.

scholarly journals Valproate serum concentrations in patients with hypoalbuminemia and medical complications

2017 ◽  
Vol 7 (1) ◽  
pp. 13-15
Author(s):  
Amy VandenBerg ◽  
Jessica Broadway ◽  
Callie Lalich ◽  
Rachel Kennedy ◽  
Kristen Williams
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Free Fraction ◽  
Serum Concentrations ◽  
Model Free ◽  
Acid Protein ◽  
Patients Experience ◽  
Patients With Epilepsy ◽  
Key Terms ◽  
Free Serum

Abstract Introduction: Valproic acid (VPA) and its derivatives are highly protein bound with free fraction increasing with dose and serum concentration. Consensus guidelines regarding dose adjustment for hypoalbuminemia are not available. Methods: A literature search was performed using PubMed to identify articles with the following key terms: “valproate,” “valproic acid,” “protein binding,” “albumin,” and “hypoalbuminemia.” We report our findings as well as 5 cases involving pharmacokinetic impact of hypoalbuminemia on valproate. Results: A previously published model for normalizing VPA serum concentration for hypoalbuminemia in patients with epilepsy was compared to results for 5 cases (4 female, 1 male) in which VPA was used for psychiatric illness. Only 1 of the cases had free serum concentrations in the range that would be expected with the model. Free concentrations ranged from 22% to 83% with no clear relationship to other factors (weight, age, serum creatinine, or dose). Female patients with similar albumin had higher free fractions than the 1 male patient. Discussion: Due to the variability in pharmacokinetic impact of hypoalbuminemia, it is important to monitor patients closely for signs of VPA toxicity in cases involving altered albumin levels. It would be prudent to use free serum VPA concentrations when patients experience fluctuations in albumin or have unexpected response to medication.

Eco-Friendly Green Liquid Chromatographic Separations of a Novel Combination of Azelastine and Fluticasone in the Presence of their Pharmaceutical Dosage form Additives

2020 ◽  
Vol 16 (3) ◽  
pp. 277-286
Author(s):  
Amal A. El-Masry ◽  
Mohammed E. A. Hammouda ◽  
Dalia R. El-Wasseef ◽  
Saadia M. El-Ashry
Keyword(s):  
Lower Limit ◽  
Dosage Form ◽  
Limit Of Detection ◽  
Sodium Dodecyl ◽  
Uv Detection ◽  
Simultaneous Estimation ◽  
Limit Of Quantification ◽  
Chromatographic Separations ◽  
Pharmaceutical Dosage Form ◽  
Liquid Chromatographic

Background: The first highly sensitive, rapid and specific green microemulsion liquid chromatographic (MELC) method was established for the simultaneous estimation of fluticasone propionate (FLU) and azelastine HCl (AZL) in the presence of their pharmaceutical dosage form additives (phenylethyl alcohol (PEA) and benzalkonium chloride (BNZ)). Methods: The separation was performed on a C18 column using (o/w) microemulsion as a mobile phase which contains 0.2 M sodium dodecyl sulphate (SDS) as surfactant, 10% butanol as cosurfactant, 1% n-octanol as internal phase and 0.3% triethylamine (TEA) adjusted at pH 6 by 0.02 M phosphoric acid; with UV detection at 220 nm and programmed with flow rate of 1 mL/min. Results: The validation characteristics e.g. linearity, lower limit of quantification (LOQ), lower limit of detection (LOD), accuracy, precision, robustness and specificity were investigated. The proposed method showed linearity over the concentration range of (0.5-25 µg/mL) and (0.1-25 µg/mL) for FLU and AZL, respectively. Besides that, the method was adopted in a short chromatographic run with satisfactory resolution factors of (2.39, 3.78 and 6.74 between PEA/FLU, FLU/AZL and AZL/BNZ), respectively. The performed method was efficiently applied to pharmaceutical nasal spray with (mean recoveries ± SD) (99.80 ± 0.97) and (100.26 ± 0.96) for FLU and AZL, respectively. Conclusion: The suggested method was based on simultaneous determination of FLU and AZL in the presence of PEA and BNZ in pure form, laboratory synthetic mixture and its combined pharmaceutical dosage form using green MELC technique with UV detection. The proposed method appeared to be superior to the reported ones of being more sensitive and specific, as well as the separation was achieved with good performance in a relatively short analysis time (less than 7.5 min). Highly acceptable values of LOD and % RSD make this method superior to be used in quality control laboratories with of HPLC technique.

Serum Concentration and Skin Expression of S100A7 (Psoriasin) in Patients Suffering from Hidradenitis Suppurativa

Dermatology ◽  
2020 ◽  
pp. 1-7
Author(s):  
Aleksandra Batycka-Baran ◽  
Wojciech Baran ◽  
Danuta Nowicka-Suszko ◽  
Maria Koziol-Gałczyńska ◽  
Andrzej Bieniek ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Hidradenitis Suppurativa ◽  
Protein Concentration ◽  
Normal Skin ◽  
Innate Immune ◽  
Antimicrobial Protein ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Reactive Protein

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. An important role of innate immune dysregulation in the pathogenesis of HS has been highlighted. S100A7 (psoriasin) is an innate, antimicrobial protein that exerts proinflammatory and chemotactic action. <b><i>Objectives:</i></b> The objective of the study was to investigate serum concentrations of S100A7 in individuals with HS as compared to healthy controls. Further, we evaluated the expression of S100A7 in lesional HS skin as compared to perilesional (clinically uninvolved) HS skin and normal skin. <b><i>Methods:</i></b> Serum concentrations of S100A7 were evaluated with a commercially available ELISA kit. The expression of S100A7 in the skin was assessed using qRT-PCR and immunofluorescence staining. <b><i>Results:</i></b> We found increased expression of S100A7 in lesional HS skin as compared to perilesional HS skin (<i>p</i> = 0.0017). The expression of S100A7 in lesional HS skin was positively associated with serum C-reactive protein concentration and the severity of disease according to Hurley staging. The serum concentration of S100A7 in individuals with HS was decreased as compared to healthy controls and patients with psoriasis. <b><i>Conclusions:</i></b> Upregulated in lesional HS skin, S100A7 may enhance the inflammatory process and contribute to the HS pathogenesis.

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