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
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Number | Mean ± SD (Range) | ||
---|---|---|---|
Mothers: | age (years) | 90 | 28 ± 5 (18–39) |
concomitant antiseizure medication | carbamazepine (mg/day) | 18 | 680 ± 291 (300–1200) |
lamotrigine (mg/day) | 12 | 246 ± 108 (100–400) | |
topiramate (mg/day) | 4 | 200 ± 0 (200–200) | |
phenytoin (mg/day) | 3 | 230 ± 125 (100–350) | |
levetiracetam (mg/day) | 2 | 750 ± 354 (500–1000) | |
primidone (mg/day) | 1 | 500 | |
phenobarbital (mg/day) | 1 | 55.5 | |
Infants: | weight (kg) | 75 | 3.2 ± 0.5 (2.0–4.3) |
length (cm) | 68 | 49 ± 2 (43–53) | |
female | 41 | ||
male | 37 |
VPA Mono Mono | Weight (kg) | Dose (mg/day) | Dose (mg/kg) | M-Cl (L/kg) | M (mg/L) | Mi (mg/L) | I (mg/L) | Mi/M Ratio | I/M Ratio |
---|---|---|---|---|---|---|---|---|---|
number | 48 | 49 | 43 | 43 | 55 | 54 | 48 | 54 | 48 |
median range | 72 52–93 | 800 150–1250 | 11.3 1.7–19.2 | 0.34 0.08–1.04 | 31.2 4.3–66.5 | 0.5 0.5–5.9 | 15.5 0.5–42.9 | 0.03 0.01–0.22 | 0.52 0.01–1.00 |
mean ± SD | 73 ± 11 | 717 ± 318 | 10.2 ± 4.6 | 0.37 ± 0.18 | 30.3 ± 13.7 | 1.2 ± 1.4 | 15.9 ± 9.7 | 0.04 ± 0.04 | 0.52 ± 0.25 |
VPA + LTG/TPM | |||||||||
number | 12 | 13 | 12 | 12 | 13 | 10 | 11 | 10 | 11 |
median range | 66 52–82 | 900 300–1500 | 12.7 4.3–20.5 | 0.38 0.24–0.60 | 37.7 14.7–47.8 | 0.5 0.5–3.0 | 14.7 6.0–24.7 | 0.02 0.01–0.09 | 0.37 0.21–1.61 |
mean ± SD | 67 ± 9 | 858 ± 385 | 13.2 ± 5.9 | 0.38 ± 0.12 | 33.7 ± 12.5 | 1.0 ± 0.9 | 13.8 ± 6.4 | 0.03 ± 0.03 | 0.49 ± 0.38 |
VPA + inducers | |||||||||
number | 18 | 18 | 14 | 14 | 22 | 20 | 19 | 20 | 19 |
median range | 74 60–113 | ** 1000 300–2250 | 16.2 4.8–25.6 | ** 0.41 0.21–0.97 | 30.1 12.8–62.1 | 0.5 0.5–3.0 | 12.7 0.5–40.3 | 0.03 0.01–0.13 | 0.44 0.03–1.12 |
mean ± SD | 76 ± 14 | 1064 ± 540 | * 15.1 ± 7.1 | 0.47 ± 0.20 | 31.8 ± 14.3 | 1.0 ± 0.9 | 14.9 ± 10.5 | 0.03 ± 0.03 | 0.48 ± 0.30 |
Total | |||||||||
number | 78 | 80 | 69 | 69 | 90 | 84 | 78 | 84 | 78 |
median range | 71 52–113 | 900 150–2250 | 12.2 1.7–25.6 | 0.36 0.08–1.04 | 31.8 4.3–66.5 | 0.5 0.5–5.9 | 14.5 0.5–42.9 | 0.03 0.01–0.22 | 0.48 0.01–1.61 |
mean ± SD | 73 ± 12 | 818 ± 409 | 11.7 ± 5.7 | 0.39 ± 0.18 | 31.2 ± 13.6 | 1.1 ± 1.2 | 15.4 ± 9.4 | 0.04 ± 0.04 | 0.51 ± 0.28 |
A | UC-d (mg/L) | I-c (mg/L) | UC/M-d Ratio | I/M-c Ratio | ||||
---|---|---|---|---|---|---|---|---|
number | 41 | 41 | 41 | 41 | ||||
median range | 41.6 10.7–72.1 | * 15.1 0.5–42.9 | 1.40 0.64–2.49 | * 0.47 0.03–1.61 | ||||
mean ± SD | 37.6 ± 16.5 | 15.8 ± 9.1 | 1.48 ± 0.45 | 0.54 ± 0.30 | ||||
delivery × colostrum | * p < 0.0001 | * p < 0.0001 | ||||||
B | I-c (mg/L) | I-m (mg/L) | Mi-c (mg/L) | Mi-m (mg/L) | I/M-c Ratio | I/M-m Ratio | Mi/M-c Ratio | Mi/M-m Ratio |
number | 21 | 21 | 19 | 19 | 21 | 21 | 19 | 19 |
median range | 14.0 0.5–26.1 | 2.3 0.5–9.5 | 0.5 0.5–5.9 | 0.5 0.5–3.0 | 0.49 0.03–1.61 | * 0.09 0.01–0.22 | 0.03 0.01–0.13 | 0.02 0.01–0.09 |
mean ± SD | 14.0 ± 8.1 | * 3.1 ± 2.9 | 1.4 ± 1.5 | 0.9 ± 0.7 | 0.52 ± 0.34 | 0.09 ± 0.07 | 0.05 ± 0.04 | 0.03 ± 0.02 |
colostrum × milk | * p < 0.0001 | not significant | * p < 0.0001 | not significant |
Ref. | N1 | Postpartum Time | Maternal Dose | M (mg/L) | Mi (mg/L) | Mi/M Ratio | N2 | I (mg/L) | I/M Ratio |
---|---|---|---|---|---|---|---|---|---|
[20] | 16 | 4.3 ± 1.1 days range 3–6 days | 22.1 ± 7.0 range 14.5–32.7 mg/kg/day | 36.4 ± 14.0 range 18.6–66.5 | 1.8 ± 1.0 range 0.4–3.9 | 0.05 ± 0.03 range 0.01–0.10 | 5 | < 1.0–13.4 | < 0.04–0.40 |
[21] | 13 | up to 12th week | 18.4 ± 7.2 mg/kg/day | 0.025 ± 0.01 | |||||
[22] | 6 | 4–19 weeks | 750–1000 mg/day | 39.4–79.0 | 6 | 0.7–1.5 | 0.01–0.02 | ||
[23] | 6 | 3–82 days | 9.5–31.0 mg/kg/day | 4.7–102.2 | 0.034–5.4 | 0.027 ± 0.015 range 0.0071–0.052 | 2 | 0.50–0.55 | |
[24] | 5 | 30.5–55.3 | 0.4–3.9 | median 0.03 range 0.01–0.07 | 1 1 | 4.4 undetectable | |||
[25] | 4 | 1st–3rd months | 1200–1500 mg/day | 0.05–0.10 | 1 | 0.08 | |||
[26] | 4 | 1st week | 1200–1800 mg/day | average 49.0 range 38.9–56.0 | average 1.8 range 1.0–3.8 | average 0.04 range 0.02–0.08 | 3 | average 28.3 range 13.0–41.0 | average 0.62 range 0.25–1.05 |
[17] | 2 | median 13 weeks range 5–20 weeks | 30.0–41.9 | 2 | 7.5 i.e., <LLOQ | median 0.21 range 0.18–0.25 | |||
[27] | 1 1 | 1.9 weeks 4.1 weeks | 500 mg/day | 1 1 | < 0.0035 < 0.005 | ||||
[28] | 1 1 | 6–17 days 1–43 days | 1000 mg/day 1400 mg/day | 1.4–3.0 1.4–3.5 | 0.02–0.03 | ||||
[29] | 1 1 | 1 month 3 months | 750 mg/day 500 mg/day | 65.0 67.0 | 1 1 | 4.0 1.0 | 0.06 0.015 | ||
[30] | 1 | 62 h 130 h | 500 mg/day | 9.9 34.3 | 0.18 0.46 | 0.02 0.01 | |||
[31] | 1 | 5 days 29 days | 1600 mg/day | 7.2 3.0 | 0.05–0.10 | 1 | 7.5 undetectable | ||
[32] | 1 | 2 months | 600 mg/day | 14.9–34.3 | < 0.4–2.0 | < 0.02–0.06 | 1 | < 0.4–2.0 | |
[33] | 1 | 2nd week | 2400 mg/day | 100.0 | 7.0 | 0.07 | |||
[34] | 1 | 3 months | 1200 mg/day | 1 | 6.6 |
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Kacirova, I.; Grundmann, M.; Brozmanova, H. 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, 13, 2074. https://doi.org/10.3390/pharmaceutics13122074
Kacirova I, Grundmann M, Brozmanova H. 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; 13(12):2074. https://doi.org/10.3390/pharmaceutics13122074
Chicago/Turabian StyleKacirova, Ivana, Milan Grundmann, and Hana Brozmanova. 2021. "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 13, no. 12: 2074. https://doi.org/10.3390/pharmaceutics13122074
APA StyleKacirova, I., Grundmann, M., & Brozmanova, H. (2021). 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, 13(12), 2074. https://doi.org/10.3390/pharmaceutics13122074