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BMC Pharmacology & Toxicology Jul 2022The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects.
METHODS
A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (C) and area under the concentration-time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded.
RESULTS
Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C, AUC and AUC of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80-1.25. A high-fat meal appeared to decrease the C and AUC of lisinopril. No severe adverse events were observed.
CONCLUSION
The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions.
TRIAL REGISTRATION
Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021).
Topics: Amlodipine; China; Chromatography, Liquid; Fasting; Healthy Volunteers; Humans; Lisinopril; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 35794660
DOI: 10.1186/s40360-022-00590-6 -
International Journal of Pharmaceutical... 2022Co-processed excipients were prepared by incorporating one excipient into the particle structure of another and a combination of two or more compendia or noncompendia...
Co-processed excipients were prepared by incorporating one excipient into the particle structure of another and a combination of two or more compendia or noncompendia excipients to physically modify their properties, which cannot be achievable by simple physical mixing. The co-processed multicomponent-based excipients were introduced to achieve better characteristics and tableting properties. This objective of this study was to develop and evaluate a co-processed excipient for amlodipine orally disintegrating tablets to simplify the compounding process. The co-processed excipients were prepared by wet granulation with 5% of polyvinylpyrrolidone and croscarmellose sodium, five different percentages of microcrystalline cellulose, and lactose monohydrate. After sieving and drying, the co-processed excipients were evaluated for flowability and compressibility. The co-processed excipients were mixed with the amlodipine powder and magnesium stearate and compressed into tablets. The amlodipine tablets were evaluated for weight variation, content uniformity, thickness, hardness, friability, disintegration, and dissolution tests. Formulation 4 was chosen as the optimum formulation because the results showed this formulation had the excellent flowability and compressibility of a co-processed excipient. It showed uniformity of weight, content, thickness, and hardness, weight loss less than 1%, fast disintegration time, and dissolution results. The developed co-processed excipient can be used by the pharmaceutical industry in the future to compound amlodipine orally disintegrating tablets in a fast and economical way.
Topics: Amlodipine; Drug Compounding; Excipients; Powders; Solubility; Tablets
PubMed: 35657749
DOI: No ID Found -
European Journal of Pharmaceutical... Jan 2021The aim of this study was to prepare pullulan-based orally disintegrating films (ODFs) containing amlodipine besylate, an anti-hypertensive drug, by the solvent casting...
The aim of this study was to prepare pullulan-based orally disintegrating films (ODFs) containing amlodipine besylate, an anti-hypertensive drug, by the solvent casting method. For this purpose, nine different ODF formulations (F1-F9) were prepared by using different plasticizers (glycerol, sorbitol, propylene glycol) and different superdisintegrants (croscarmellose sodium, sodium starch glycolate, crospovidone). FD&C Green and aspartame were used as coloring agent and sweetener, respectively. According to the results of preformulation studies, the optimum ODF (F9) was determined and various characterization studies such as uniformity of mass, film thickness, surface pH of films, and mechanical properties (such as elongation at break, tensile strength, Young's modulus, and folding endurance), moisture content, disintegration time, uniformity of content and dissolution test, X-ray, DSC, SEM and short term stability analysis were performed on this formulation. Cytotoxicity and permeability studies for the F9 formulation were performed on the human epithelial colorectal adenocarcinoma (Caco-2) cell line. The formulation F9 had appropriate morphological and mechanical properties and disintegrated within 51.3 s according to the petri dish method, and 28.8 s according to the drop method. Dissolution studies revealed that 78.1 % of amlodipine besylate was dissolved in 20 min from F9 formulation. Cell culture studies showed that the formulation had no significant toxic effect on the Caco-2 cells. Also, there was no significant difference between the Caco-2 permeabilities of amlodipine besylate powder and amlodipine besylate ODFs. As a result of all these studies, we suggest to use the pullulan based amlodipine besylate ODFs to enhance ease of administration and patient compliance.
Topics: Administration, Oral; Amlodipine; Caco-2 Cells; Glucans; Humans; Solubility
PubMed: 33065224
DOI: 10.1016/j.ejps.2020.105597 -
Expert Opinion on Pharmacotherapy Aug 2021: A fixed-dose combination of amlodipine and celecoxib, branded in the USA as Consensi®, was recently granted a US Food and Drug Administration (FDA)-approved...
: A fixed-dose combination of amlodipine and celecoxib, branded in the USA as Consensi®, was recently granted a US Food and Drug Administration (FDA)-approved indication for treatment of comorbid hypertension and osteoarthritis.: A PubMed and Medline search was conducted for clinical trials published through December 2020 in the English language using keywords amlodipine, celecoxib, combination product, consensi, hypertension, osteoarthritis, and pill burden. Although no clinical trials have been published in the peer-reviewed literature, results from two phase 3 clinical trials reported to ClinicalTrials.gov suggest that amlodipine-celecoxib has similar short-term efficacy compared with amlodipine alone in reducing blood pressure and a comparable adverse event profile to the individual components administered alone.: Despite the pill burden reduction and a body of evidence supporting the efficacy and safety of the individual drugs, the role of amlodipine-celecoxib in the management of patients with hypertension-osteoarthritis remains in question. This is in no small part because the combination product is very costly relative to the generic components, provides limited flexibility for dose-adjustment, and lacks long-term data on safety and efficacy.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Celecoxib; Drug Combinations; Humans; Hypertension; Osteoarthritis; Pain
PubMed: 33938788
DOI: 10.1080/14656566.2021.1915289 -
Blood Pressure Apr 2021In a randomised, double-blind trial, we investigated effects of lacidipine on clinic and ambulatory blood pressure (BP) and arterial stiffness in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
In a randomised, double-blind trial, we investigated effects of lacidipine on clinic and ambulatory blood pressure (BP) and arterial stiffness in patients with mild-to-moderate hypertension, as compared with amlodipine.
MATERIALS AND METHODS
Previously untreated and treated patients ( = 269, 50-80 years of age) with clinic hypertension (a clinic systolic/diastolic BP 140-180/<110 mmHg and <160/100 mmHg, respectively) were randomly assigned to double-dummy treatment with lacidipine (4-6 mg/day) or amlodipine (5-7.5 mg/day) for 20 weeks. The primary efficacy variable was the change in 24-h ambulatory systolic BP at 20 weeks of treatment. Arterial stiffness was measured as brachial-ankle pulse wave velocity (PWV).
RESULTS
After 20 weeks of treatment, 24-h systolic BP decreased from 141.3 ± 14.0 and 138.3 ± 12.8 mmHg at baseline, respectively, in the lacidipine ( = 134) and amlodipine groups ( = 135), by a least square mean (±SE) change of 15.2 ± 1.3 and 15.5 ± 1.3 mmHg, respectively, with a between-group difference (95% confidence interval [CI]) of 0.3 mmHg (-3.4 to 4.1, = 0.86). Similar results were observed for other ambulatory BP components and clinic BP. Clinic and ambulatory pulse rate did not significantly change in either group ( ≥ 0.21). PWV decreased significantly ( < 0.001) from baseline in both groups, with a non-significant between-group difference of 0.24 m/s ( = 0.45). The incidence rate of adverse events was 30.3% ( = 40) and 27.5% ( = 36) in the lacidipine and amlodipine groups, respectively ( = 0.61). No serious adverse event occurred in the trial.
CONCLUSIONS
Lacidipine effectively lowers clinic and ambulatory BP in patients with mild-to-moderate hypertension and significantly improves arterial stiffness, similarly as amlodipine.
Topics: Aged; Aged, 80 and over; Amlodipine; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dihydropyridines; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Vascular Stiffness
PubMed: 33135429
DOI: 10.1080/08037051.2020.1840915 -
Current Drug Metabolism 2020The present article is related to in-vitro and in-vivo herb-drug interaction studies.
BACKGROUND
The present article is related to in-vitro and in-vivo herb-drug interaction studies.
OBJECTIVES
This study aimed to investigate the effect of Nigella sativa and fenugreek on the pharmacodynamics and pharmacokinetics of amlodipine.
METHOD
Hypertensive rats of group-I were treated with amlodipine and rats of group-II and III were treated with N. sativa, and N. sativa + amlodipine and fenugreek, and fenugreek + amlodipine, respectively. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of group-I, II and III rats were measured by the "tail-cuff system".
RESULTS
N. sativa, as well as fenugreek, reduced the SBP, DBP and MBP. Simultaneously, administration of fenugreek + amlodipine or N. sativa + amlodipine showed better control of BP. Individually, fenugreek, as well as N. sativa, showed a surprising reduction in the heart rate. There was no remarkable effect of any of these two herbs on Cmax, AUC0-t, Kel, and terminal elimination half-life of amlodipine, but fenugreek altered the Tmax of amlodipine significantly, from 2 ± 1.2h in control to 7.2 ± 1.7h in fenugreek treated group, probably by delaying the absorption.
CONCLUSION
Results of pharmacodynamics and pharmacokinetics studies suggested that simultaneous administration of fenugreek or N. sativa with amlodipine improved the pharmacological response of amlodipine in hypertensive rats, though there was no remarkable change in pharmacokinetic parameters (Cmax, Kel, elimination t1/2, and AUC0-t).
Topics: Amlodipine; Animals; Antihypertensive Agents; Blood Pressure; Herb-Drug Interactions; Hypertension; Male; Models, Animal; Nigella sativa; Plant Extracts; Rats; Rats, Wistar; Trigonella
PubMed: 32407268
DOI: 10.2174/1389200221666200514121501 -
Current Medical Research and Opinion Dec 2023To provide clinical characteristics and to quantify the number of patients receiving the extemporaneous combination of the calcium channel blocker amlodipine and the... (Observational Study)
Observational Study
OBJECTIVES
To provide clinical characteristics and to quantify the number of patients receiving the extemporaneous combination of the calcium channel blocker amlodipine and the angiotensin converting enzyme inhibitor zofenopril in a real-world setting. This evidence can provide a snapshot of the potential users of the two molecules in a single pill combination (SPC).
METHODS
Retrospective observational study using data from the IQVIA Italian Longitudinal Patient Database. Adult patients firstly prescribed with amlodipine and zofenopril between 1 July 2011 and 30 June 2020 were identified and demographic and clinical characteristics were extracted. Treatment adherence was evaluated as proportion of days covered (PDC). The potential number of patients eligible for a SPC was calculated.
RESULTS
A population of 2394 hypertensive patients, mean age of 68.6 years ±12.7, 52.6% male were treated with amlodipine and zofenopril. The majority of patients (54.5%) were low adherent (PDC <40%), 25.9% were intermediate adherent and only 19.6% were high adherent (>80%) to therapy. Around 42,500 adult hypertensive patients were estimated to be prescribed the extemporaneous combination in 2019 in Italy, being potentially eligible for treatment with amlodipine and zofenopril SPC.
CONCLUSIONS
The administration of the extemporaneous combination of zofenopril and amlodipine in hypertensive patients is a common practice in Italy. The development of a SPC can be a viable treatment option to simplify therapy and to increase adherence in hypertensive patients who are already on the two monotherapies in combination.
Topics: Adult; Humans; Male; Aged; Female; Amlodipine; Antihypertensive Agents; Hypertension; Data Analysis; Blood Pressure; Drug Combinations; Drug Therapy, Combination
PubMed: 36946189
DOI: 10.1080/03007995.2023.2192607 -
Pharmaceutical Biology Dec 2020Hyperlipidaemia and hypertension are often treated together with curcumin and amlodipine. It is necessary to investigate the drug-drug interaction between curcumin and...
Hyperlipidaemia and hypertension are often treated together with curcumin and amlodipine. It is necessary to investigate the drug-drug interaction between curcumin and amlodipine. The interaction between curcumin and amlodipine was investigated in rats and with rat liver microsomes. The pharmacokinetics of amlodipine (1 mg/kg) was investigated in rats with or without curcumin pre-treatment (2 mg/kg), six rats in each group. The metabolic stability of amlodipine was investigated with rat liver microsomes. Curcumin significantly increased the (26.19 ± 2.21 versus 17.80 ± 1.56 μg/L), (507.27 ± 60.23 versus 238.68 ± 45.59 μg·h/L), and (14.69 ± 1.64 versus 11.43 ± 1.20 h) of amlodipine ( < 0.05). The metabolic stability of amlodipine was significantly increased with the half-life time in rat liver microsomes increased from 34.23 ± 3.33 to 44.15 ± 4.12 min, and the intrinsic rate decreased from 40.49 ± 3.26 to 31.39 ± 2.78 μL/min/mg protein. These results indicated that drug-drug interaction might appear during the co-administration of curcumin and amlodipine. The potential mechanism may be due to the inhibition of CYP3A4 by curcumin. Thus, this interaction should be given special attention in the clinic and needs further experiments to characterize the effect in humans.
Topics: Amlodipine; Animals; Curcumin; Drug Interactions; Male; Microsomes, Liver; Rats; Rats, Sprague-Dawley
PubMed: 32432949
DOI: 10.1080/13880209.2020.1764060 -
Journal of Artificial Organs : the... Jun 2020A young male presented in refractory shock from amlodipine poisoning despite vasopressors, insulin-normoglycemia therapy, calcium gluconate and glucagon. He needed...
A young male presented in refractory shock from amlodipine poisoning despite vasopressors, insulin-normoglycemia therapy, calcium gluconate and glucagon. He needed venoarterial ECMO for hemodynamic support and TPE to remove protein-bound amlodipine. The use of extracorporeal membrane oxygenation (ECMO) for cardiotoxic poisoning and Total Plasma Exchange (TPE) in removing drugs has been described in the literature. We report a rare case where both lifesaving extracorporeal therapies were used in a patient with a severe drug overdose. Stabilizing hemodynamics with ECMO combined with TPE for drug removal is a feasible strategy in unstable patients with amlodipine overdose.
Topics: Adult; Amlodipine; Calcium Channel Blockers; Drug Overdose; Extracorporeal Membrane Oxygenation; Hemodynamics; Humans; Male; Plasma Exchange; Respiration, Artificial; Treatment Outcome
PubMed: 31552515
DOI: 10.1007/s10047-019-01132-4 -
Journal of Clinical Hypertension... Sep 2023The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.
The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).
Topics: Humans; Rosuvastatin Calcium; Atorvastatin; Amlodipine; Hypertension; Cholesterol, LDL; Dyslipidemias; Leukemia, Myeloid, Acute; Double-Blind Method; Treatment Outcome
PubMed: 37584254
DOI: 10.1111/jch.14715