- A New Validated HPLC Method for the Determination of Levodopa: Application to Study the impact of ketogenic diet on the Pharmacokinetics of Levodopa in Parkinson's Participants. [Journal Article]
- BCBiomed Chromatogr 2018 Sep 11; :e4382
- A simple, accurate, and reproducible HPLC-UV method has been developed and validated for the quantification of levodopa (L-Dopa) in human plasma. The method involves a simple protein precipitation pr...
A simple, accurate, and reproducible HPLC-UV method has been developed and validated for the quantification of levodopa (L-Dopa) in human plasma. The method involves a simple protein precipitation procedure to extract both L-Dopa and methyldopa, the internal standard. The chromatographic analysis was achieved on a Shimadzu LC 20A HPLC system equipped with a Zorbax Eclipse XDB C18 column and an isocratic mobile phase consisted of 20 mM KH2 PO4 (pH 2.5) and methanol (95:5, v/v) run at a flow rate of 1 ml/min. The UV detection wavelength was set at 230 nm. The method exhibited good linearity (R2 > 0.999) over the assayed concentration range (0.1-10 μg/mL) and demonstrated good intra-day and inter-day precision and accuracy (relative standard deviations and the deviation from predicted values were less than 15%). This method was also successfully applied for studying the potential effect of ketogenic diet on the pharmacokinetics of L-Dopa in Parkinson's participants. Our data analysis indicates that ketogenic diet does not significantly affect the pharmacokinetics of L-Dopa.
- Increased rate of birth defects after first trimester use of angiotensin converting enzyme inhibitors - Treatment or hypertension related? An observational cohort study. [Journal Article]
- PHPregnancy Hypertens 2018; 13:65-71
- CONCLUSIONS: Women with hypertension treated with ACEIs in early pregnancy are at higher risk for major birth defects, which may be explained by other factors associated with maternal hypertension. Women (inadvertently) exposed during early pregnancy may be reassured and treatment switched to antihypertensive drugs recommended for pregnancy.
- Polymethyldopa Nanoparticles-Based Fluorescent Sensor for Detection of Tyrosinase Activity. [Journal Article]
- ASACS Sens 2018 Sep 11
- Being a typical copper-containing oxidase, tyrosinase plays critical roles in biological activity, and its aberrant expression might cause diverse skin diseases. Herein, we, for the first time, have ...
Being a typical copper-containing oxidase, tyrosinase plays critical roles in biological activity, and its aberrant expression might cause diverse skin diseases. Herein, we, for the first time, have found an interesting green fluorogenic reaction between methyldopa and ethanolamine. By combining transmission electron microscopy, UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and MALDI-TOF mass spectrum analysis, we have confirmed that there is a reliable method for preparing the bright green fluorescent polymethyldopa nanoparticles (PMNPs) by simply mixing methyldopa and ethanolamine at room temperature. Inspired by such a simple and convenient fluorogenic reaction, a novel polymethyldopa nanoparticles-based fluorescent sensor for detection of tyrosinase activity was developed by using the commercially available metyrosine as a substrate, accompanied by the tyrosinase-catalyzed specific conversion of metyrosine into methyldopa. According to the intrinsic sensitivity/selectivity of fluorescence technology and unambiguous response mechanism, our fluorescent sensor exhibits excellent sensing performance and can be utilized in the determination of the tyrosinase activity in real biological samples and inhibitor screening.
- Enzyme Replacement Therapy During Pregnancy in Fabry Patients : Review of Published Cases of Live Births and a New Case of a Severely Affected Female with Fabry Disease and Pre-eclampsia Complicating Pregnancy. [Journal Article]
- JRJIMD Rep 2018 Aug 17
- Fabry disease (FD) is an X-linked, lysosomal storage disease. Mutations in the gene coding for alpha-galactosidase A lead to globotriaosylceramide (Gb-3) accumulation in lysosomes and in placenta and...
Fabry disease (FD) is an X-linked, lysosomal storage disease. Mutations in the gene coding for alpha-galactosidase A lead to globotriaosylceramide (Gb-3) accumulation in lysosomes and in placenta and umbilical cord. Impact of FD and treatment with enzyme replacement (ERT) on foetal development is undisclosed.A 38-year-old primigravida with FD (G85N) is reported. She has 50% reduced alpha-galactosidase A activity and elevated plasma and urine-Gb-3. She was severely affected with ischaemic stroke at age 23, hypertension, albuminuria and moderately reduced renal function. ERT was initiated at age 23 years in 2001 and continued during spontaneous pregnancy at age 38. In third trimester she developed moderate-to-severe pre-eclampsia, successfully managed by methyldopa. Chorion villus sampling revealed a male foetus without the maternal gene mutation. Planned Caesarean section was performed without complications at gestational age week 38 + 6, delivering a healthy boy. Histopathological placental examination showed no sign of Gb-3 accumulation. Literature survey disclosed a total of 12 cases, 8 were treated with ERT during pregnancy and 5 infants inherited the family mutation. All outcomes were successful. In the six cases with available placental histopathological examination, Gb-3 accumulation was only seen on the foetal side if the foetus had the inherited mutation.In conclusion, the present case, describing the first data from a severely affected FD patient receiving ERT during pregnancy complicated by pre-eclampsia, together with all other published cases, has emphasized that ERT is safe during pregnancy and resulting in successful foetal outcome; despite this, ERT is by the health authorities advised against during pregnancy.
- Drugs and Lactation Database (LactMed) [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- Because of the low levels of methyldopa in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. No special precautions are...
Because of the low levels of methyldopa in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. No special precautions are required.
- Pharmacokinetics, metabolism and safety of deuterated L-DOPA (SD-1077)/carbidopa compared to L-DOPA/carbidopa following single oral dose administration in healthy subjects. [Journal Article]
- BJBr J Clin Pharmacol 2018 Jun 29
- CONCLUSIONS: SD-1077/CD demonstrated the potential to prolong exposure to central DA at comparable peripheral PK and safety to the reference L-DOPA/CD combination. A single dose of SD-1077 is safe for further clinical development in Parkinson's disease patients.
- Resistant Hypertension in Pregnancy: How to Manage? [Review]
- CHCurr Hypertens Rep 2018 Jun 11; 20(8):63
- The concept of resistant hypertension may be changed during pregnancy by the physiological hemodynamic changes and the particularities of therapy choices in this period. This review discusses the man...
The concept of resistant hypertension may be changed during pregnancy by the physiological hemodynamic changes and the particularities of therapy choices in this period. This review discusses the management of pregnant patients with preexisting resistant hypertension and also of those who develop severe hypertension in gestation and puerperium.
- Antidepressant use during pregnancy and the risk of developing gestational hypertension: a retrospective cohort study. [Journal Article]
- BPBMC Pregnancy Childbirth 2018 May 29; 18(1):187
- CONCLUSIONS: Prolonged use of antidepressants during the first 20 weeks of gestation appeared to be associated with an increased risk of developing gestational hypertension. When balancing the benefits and risks of using these drugs during pregnancy, this should be taken into account.
- Micellar HPLC-UV method for the simultaneous determination of levodopa, carbidopa and entacapone in pharmaceuticals and human plasma. [Journal Article]
- JCJ Chromatogr B Analyt Technol Biomed Life Sci 2018 Aug 01; 1091:36-45
- A method based on micellar liquid chromatography to quantify levodopa, carbidopa and entacapone in plasma is reported. The sample pretreatment was a simple dilution in a pure micellar solution then f...
A method based on micellar liquid chromatography to quantify levodopa, carbidopa and entacapone in plasma is reported. The sample pretreatment was a simple dilution in a pure micellar solution then filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 7 min, using an aqueous solution of 0.1 M sodium dodecyl sulphate-10% n-propanol-0.3 tiethylamine, adjusted at pH 2.8 with 0.02 M orthophosphoric acid as mobile phase, running under isocratic mode at 1.0 mL/ min through VP-ODS column. The detection was done by UV (ultraviolet) absorbance at 225 nm. The method was successfully validated by the International Conference Harmonization guidelines in terms of: selectivity, linearity (r2 > 0.998) over the concentration ranges of 0.025-1.2, 0.05-1.0 and 0.3-2.0 μg mL-1 with limits of detection of 0.01, 6.16 × 10-3 and 0.02 μg mL-1 and limits of quantification of 0.03, 0.02 and 0.07 μg mL-1 for levodopa, carbidopa and entacapone, respectively. The proposed method was applied successfully for quantification of the studied drugs in their different dosage forms. Moreover, the method was further extensive to the quantification of the studied drugs in spiked human plasma and was successfully validated by the guidelines of the European Medicines Agency. The proposed procedures were successfully evaluated to determine the studied drugs in real human plasma. The procedure was found reliable, practical, cost-effective, available, short period, easy-to-handle, low-cost, environmental-friendly, secure, useful for the analysis of numerous samples per day. Lastly, the method was performed to the analysis of incurred, using quality control samples in the same analytical run, with adequate results. Therefore, it can be implementable for custom analysis in clinical laboratories.
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- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Alpha-adrenergic agonist toxicity is due to a broad group of pharmaceutical agents known as alpha agonists, which can be further broken down into central alpha-2 agonists and peripheral alpha-1 agoni...
Alpha-adrenergic agonist toxicity is due to a broad group of pharmaceutical agents known as alpha agonists, which can be further broken down into central alpha-2 agonists and peripheral alpha-1 agonists. Central alpha-2 agonists include clonidine, guanfacine, tizanidine, guanabenz, and methyldopa. Peripheral alpha-1 agonists include imidazoline, oxymetazoline, tetrahydrozoline, and naphazoline. Mainly there are 2 alpha receptors of pharmacological significance – central alpha-2 and peripheral alpha-1 adrenergic receptors. Stimulation of central alpha-2 receptors causes decreased secretion of catecholamines through a negative feedback mechanism. Stimulation of peripheral alpha-1 receptors primarily increases blood pressure via induced vasoconstriction. Alpha-adrenergic agonist toxicity is of primary concern with alpha-2 adrenergic agonist xenobiotics through the resulting depletion of catecholamines associated with these agents; however, there are many topical alpha-1 agonists that when misused cause similar toxicity. Toxicity is encountered in various populations, particularly in children and adolescents, due to the growing use of these agents. Toxicity is associated with a compilation of symptoms, including central nervous system depression, bradycardia, and hypotension. Alpha-adrenergic toxicity is often very responsive to supportive care, including intravenous fluid administration, airway monitoring, and repletion of catecholamines as necessary via the use of vasopressor agents. There is no antidote approved for human use, and naloxone has no proven efficacy.