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Journal of Chromatography. B,... Feb 2016An ultra high pressure liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method for the simultaneous quantitation of pravastatin and major metabolites,...
An ultra high pressure liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method for the simultaneous quantitation of pravastatin and major metabolites, 3'α-hydroxy-pravastatin, pravalactone and 3'α-hydroxy-pravalactone, in human plasma has been developed and validated. Aliquots of (100μL) plasma in EDTA were diluted in pH 4.5 (0.1M buffer) to stabilize the analytes and subjected to hydrophilic lipophilic balance (HLB) solid phase extraction on 96 well μelution plates. Extracted samples were evaporated to dryness and reconstituted in pH 4.5 buffer. Chromatographic separation was performed on a Cortecs™ C18 column (2.1×100mm, 1.8μm), using gradient elution with a blend of acetonitrile and 10mM methylammonium acetate buffer (pH 4.5) at a flow rate of 0.4mL/min. Mass spectrometric detection was performed using multiple reaction monitoring (MRM) switching between positive/negative electrospay ionization (ESI). Pravastatin, 3'α-hydroxy-pravastatin, and internal standards [(2)H3]-pravastatin, and [(2)H3]-3'α-hydroxy-pravastatin were monitored in negative ESI mode at ion transitions m/z 423.2→321.1 and 426.2→321.1, respectively. Positive ESI mode was used for the detection of pravalactone, 3'α-hydroxy-pravalactone, and internal standards [(2)H3]-pravalactone, and [(2)H3]-3'α-hydroxy-pravalactone at ion transitions m/z 438.2→183.1 and 441.2→269.1 respectively. The method was linear for all analytes in the concentration range 0.5-200nM with intra- and inter-day precisions (as relative standard deviation) of ≤5.2% and accuracy (as relative error) of ≤8.0% at all quality control levels. The method was successfully applied to the investigation of pharmacokinetic properties of pravastatin and its metabolites in children after an oral dose of 20-40mg.
Topics: Adolescent; Child; Chromatography, High Pressure Liquid; Female; Humans; Isomerism; Lactones; Linear Models; Male; Pravastatin; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry
PubMed: 26849185
DOI: 10.1016/j.jchromb.2016.01.038 -
Clinical Neuropharmacology Dec 1993
Clinical Trial
Topics: Anticholesteremic Agents; Humans; Lovastatin; Pravastatin
PubMed: 9377592
DOI: 10.1097/00002826-199312000-00010 -
General Physiology and Biophysics Jul 2021Skeletal muscle secrets several bioactive molecules known as myokines. Interleukin-6 (IL-6) has been described as a myokine secreted in response to skeletal muscle...
Skeletal muscle secrets several bioactive molecules known as myokines. Interleukin-6 (IL-6) has been described as a myokine secreted in response to skeletal muscle injury as well as to macrophage invasion in inflammation. To our knowledge no connection between macrophages and skeletal muscle regarding IL-6 secretion has been described so far. Here we report that co-culturing of C2C12 cells with RAW macrophages enhances IL-6 secretion of the cells cultured together. However, this is not seen in cross-feeding experiments, where culture medium of RAW macrophage culture is used as the culture medium of C2C12 cells or vice versa. Pravastatin, known to induce myopathy, also stimulates IL-6 production in monocultured C2C12 cells and elevates IL-6 concentration in the culture medium of the co-cultures. These results indicate an intricate interaction between skeletal muscle and macrophages in inflammation related to IL-6 production.
Topics: Humans; Inflammation; Interleukin-6; Macrophages; Muscle, Skeletal; Pravastatin
PubMed: 34350835
DOI: 10.4149/gpb_2021017 -
Journal of Clinical Pharmacology Feb 1995The bioavailability of pravastatin, a hypocholesterolmic agent, may be enhanced by decreasing its exposure to stomach contents, where it may be converted... (Clinical Trial)
Clinical Trial
The bioavailability of pravastatin, a hypocholesterolmic agent, may be enhanced by decreasing its exposure to stomach contents, where it may be converted nonenzymatically to a relatively inactive metabolite. The pharmacokinetics of pravastatin and its metabolite were determined after infusion of pravastatin directly into the stomach (locus for greatest bioavailability for the metabolite), duodenum (greatest bioavailability for pravastatin), jejunum, or ileum. An enterically coated formulation of pravastatin may increase its bioavailability.
Topics: Adult; Biological Availability; Drug Administration Schedule; Duodenum; Gastric Mucosa; Humans; Ileum; Intestinal Absorption; Intubation, Gastrointestinal; Jejunum; Male; Pravastatin
PubMed: 7751423
DOI: 10.1002/j.1552-4604.1995.tb05002.x -
FDA Consumer 2006
Topics: Anticholesteremic Agents; Drugs, Generic; Humans; Hyperlipidemias; Pravastatin
PubMed: 17243278
DOI: No ID Found -
Recenti Progressi in Medicina May 1995A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3-hydroxy-3 methylglutaril coenzyme A reductase inhibitor, is reported....
A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3-hydroxy-3 methylglutaril coenzyme A reductase inhibitor, is reported. The patient, a 69-year-old man was affected by non-insulin-dependent diabetes mellitus and hypertension. He assumed pravastatin (20 mg/day) because of hypercholesterolemia. He was admitted with acute myopathy of the lower limbs which resolved in a few days after pravastatin discontinuation. A previously unknown hypothyroidism, probably due to chronic autoimmune thyroiditis, was evidenced. Muscle biopsy (left gastrocnemius) revealed a perimysial and endomysial inflammatory infiltrate with a prevalence of CD4+ lymphocytes. While lovastatin and simvastatin have been associated with toxic myopathy, pravastatin-associated myopathy could represent a distinct, inflammatory entity.
Topics: Acute Disease; Aged; Biopsy; Diabetes Mellitus, Type 2; Humans; Hypercholesterolemia; Hypertension; Male; Muscle, Skeletal; Muscular Diseases; Myositis; Pravastatin
PubMed: 7604176
DOI: No ID Found -
American Journal of Obstetrics and... Jun 2016Preeclampsia complicates approximately 3-5% of pregnancies and remains a major cause of maternal and neonatal morbidity and mortality. It shares pathogenic similarities... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Preeclampsia complicates approximately 3-5% of pregnancies and remains a major cause of maternal and neonatal morbidity and mortality. It shares pathogenic similarities with adult cardiovascular disease as well as many risk factors. Pravastatin, a hydrophilic, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor, has been shown in preclinical studies to reverse various pathophysiological pathways associated with preeclampsia, providing biological plausibility for its use for preeclampsia prevention. However, human trials are lacking.
OBJECTIVE
As an initial step in evaluating the utility of pravastatin in preventing preeclampsia and after consultation with the US Food and Drug Administration, we undertook a pilot randomized controlled trial with the objective to determine pravastatin safety and pharmacokinetic parameters when used in pregnant women at high risk of preeclampsia.
STUDY DESIGN
We conducted a pilot, multicenter, double-blind, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12(0/7) and 16(6/7) weeks' gestation were assigned to daily pravastatin 10 mg or placebo orally until delivery. Primary outcomes were maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included rates of preeclampsia and preterm delivery, gestational age at delivery, birthweight, and maternal and cord blood lipid profile (clinicaltrials.gov identifier NCT01717586).
RESULTS
Ten women assigned to pravastatin and 10 to placebo completed the trial. There were no differences between the 2 groups in rates of study drug side effects, congenital anomalies, or other adverse or serious adverse events. There was no maternal, fetal, or neonatal death. Pravastatin renal clearance was significantly higher in pregnancy compared with postpartum. Four subjects in the placebo group developed preeclampsia compared with none in the pravastatin group. Although pravastatin reduced maternal cholesterol concentrations, umbilical cord cholesterol concentrations and infant birthweight were not different between the groups. The majority of umbilical cord and maternal pravastatin plasma concentrations at the time of delivery were below the lower limit of quantification of the assay. Pravastatin use was associated with a more favorable pregnancy angiogenic profile.
CONCLUSION
This study provides preliminary safety and pharmacokinetic data regarding the use of pravastatin for preventing preeclampsia in high-risk pregnant women. Although the data are preliminary, no identifiable safety risks were associated with pravastatin use in this cohort. This favorable risk-benefit analysis justifies using pravastatin in a larger clinical trial with dose escalation.
Topics: Adult; Birth Weight; Cholesterol; Double-Blind Method; Female; Fetal Blood; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Infant, Newborn; Pilot Projects; Pravastatin; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy, High-Risk
PubMed: 26723196
DOI: 10.1016/j.ajog.2015.12.038 -
Journal of Clinical Gastroenterology Sep 1997Pravastatin dissolves gallstones in patients with hypercholesterolemia by reducing the cholesterol saturation index (CSI) of bile. There are few reports on effect of...
Pravastatin dissolves gallstones in patients with hypercholesterolemia by reducing the cholesterol saturation index (CSI) of bile. There are few reports on effect of pravastatin on bile lipids, CSI and nucleation time (NT) in patients with gallstones and normal plasma lipid levels, or on the effect of pravastatin on gallbladder motility. Therefore we studied the effect of pravastatin on bile lipids, CSI, NT, and gallbladder motility in persons with normal cholesterol levels. We included 10 patients (ages 32 +/- 8 years; 6 men) with symptomatic gallstones and normal plasma lipid profiles. Estimation of bile lipids, CSI, and NT in duodenal bile and gallbladder motility were done using standard methods. Subsequently each patient was given 40 mg pravastatin daily for 1 month. At completion of pravastatin therapy, bile lipids and gallbladder motility studies were repeated. After pravastatin therapy, we found no significant reduction in bile cholesterol (11.2 +/- 3.2 vs. 10.4 +/- 2.8 mmol/l), bile acids (114.6 +/- 7.4 vs. 133 +/- 16 mmol/l), phospholipids (23 +/- 3.5 vs. 24 +/- 6.2 mmol/l), CSI (1.28 +/- 0.4 vs. 1.22 +/- 0.3), and nucleation time (7 +/- 3 vs. 7 +/- 3 days). In addition, there was no significant change in gallbladder fasting volume (26 +/- 3 vs. 26.6 +/- 3 ml), residual volume (14.6 +/- 1.1 vs. 15.08 +/- 1.4 ml), ejection fraction (44% vs. 43%), and rate constant of gallbladder emptying (0.018/min vs. 0.022/min). One-month therapy with pravastatin does not alter bile lipids, CSI, NT, and gallbladder contractility in persons with normal levels of cholesterol.
Topics: Adult; Bile; Cholelithiasis; Cholesterol; Female; Gallbladder; Gallbladder Emptying; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pravastatin; Reference Values
PubMed: 9412944
DOI: 10.1097/00004836-199709000-00007 -
Clinical Therapeutics May 2016Remnant lipoproteins cholesterol are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed....
Remnant lipoproteins cholesterol are products of partially catabolized chylomicrons and very-low-density lipoprotein, from which some triglycerides have been removed. These particles are smaller and are believed to be strongly atherogenic. Elevated Remnant lipoproteins cholesterol levels were reported to be associated with endothelial dysfunction and atherosclerotic disease.
Topics: Atherosclerosis; Cholesterol; Dyslipidemias; Humans; Pravastatin; Triglycerides
PubMed: 27041404
DOI: 10.1016/j.clinthera.2016.03.019 -
Biomedical Chromatography : BMC Apr 2016This report describes the development and validation of a chromatography/tandem mass spectrometry method for the quantitative determination of pravastatin and its... (Clinical Trial)
Clinical Trial
This report describes the development and validation of a chromatography/tandem mass spectrometry method for the quantitative determination of pravastatin and its metabolite (3α-hydroxy pravastatin) in plasma and urine of pregnant patients under treatment with pravastatin, as part of a clinical trial. The method includes a one-step sample preparation by liquid-liquid extraction. The extraction recovery of the analytes ranged between 93.8 and 99.5% in plasma. The lower limits of quantitation of the analytes in plasma samples were 0.106 ng/mL for pravastatin and 0.105 ng/mL for 3α-hydroxy pravastatin, while in urine samples they were 19.7 ng/mL for pravastatin and 2.00 ng/mL for 3α-hydroxy pravastatin. The relative deviation of this method was <10% for intra- and interday assays in plasma and urine samples, and the accuracy ranged between 97.2 and 106% in plasma, and between 98.2 and 105% in urine. The method described in this report was successfully utilized for determining the pharmacokinetics of pravastatin in pregnant patients enrolled in a pilot clinical trial for prevention of preeclampsia.
Topics: Anticholesteremic Agents; Chromatography, High Pressure Liquid; Female; Humans; Limit of Detection; Liquid-Liquid Extraction; Pravastatin; Pregnancy; Tandem Mass Spectrometry
PubMed: 26360932
DOI: 10.1002/bmc.3581