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Real-World Data and Real-World Evidence
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
Finally, 48053 eligible patients newly prescribed with telmisartan and 4665 patients with ramipril were included. To control for confounders, propensity score (PS) was calculated based on 74 patient characteristics including demographics, comorbid conditions, concurrent medications, and health care use measures, and then PS matching (1:1) with a caliper of 0.05 was used to balance patient characteristics83. Standardized differences were compared to evaluate the balance level after PS matching. An unstratified Cox proportional hazards regression was applied to compute hazard ratios (HRs) and 95% CIs, whose robustness was assessed by replicating it in a larger cohort derived with less stringent exclusion criteria83.
Cardiovascular Drugs
Published in Radhwan Nidal Al-Zidan, Drugs in Pregnancy, 2020
Risk Summary: Telmisartan is contraindicated during the 2nd and 3rd Trimesters because the pregnancy experience in humans showed a profound potentiality of teratogenicity and severe fetal toxicity associated with its use during this period.
Antihypertensive Drug Classes
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Engi Abdel-Hady Algharably, Reinhold Kreutz
The bioavailability of ARBs ranges from 13% for eprosartan to about 60% for irbesartan and telmisartan. Losartan undergoes first-pass metabolism in the liver via the cytochrome P450 (CYP) system to form EXP3174, which is more potent than parenteral losartan. Protein binding for all ARBs is high, but they vary widely in their volume of distribution from 10 L for candesartan to 500 L for telmisartan. ARBs exhibit considerably different plasma half-lives, although this does not necessarily correlate with the duration of their BP-lowering effect (Table 40.2). Contrary to ACE inhibitors, the mode of elimination for ARBs is predominantly hepatic; therefore, no dosage adjustment based on pharmacokinetic rationales is required in patients with impaired renal function (7). Losartan has a potential for drug interactions due to its metabolism by CYP2C9, which is important to generate EXP-3174. Inhibition of this enzyme with concomitant drugs (e.g. azole antimycotics) will increase losartan levels but decrease EXP-3174, while inducers like rifampin will increase the clearance of both losartan and EXP3174. Telmisartan may cause variable increases in serum digoxin levels, mandating monitoring digoxin levels during concomitant therapy (2).
Selection of the candidate compound at an early stage of new drug development: retrospective pharmacokinetic and metabolic evaluations of valsartan using common marmosets
Published in Xenobiotica, 2022
Shogo Matsumoto, Shotaro Uehara, Hidetaka Kamimura, Naoki Cho, Hiroshi Ikeda, Satoshi Maeda, Kensuke Kagiyama, Atsunori Miyata, Hiroshi Suemizu, Kazumasa Fukasawa
The t1/2, pred values of valsartan and telmisartan (10.0 and 22.9 h, respectively) suggested that the two compounds would exhibit elimination t1/2 values suitable for once daily dosing with oral drugs (generally 12–48 h, Smith et al. 2018). The low CLt value of valsartan contributed to its high t1/2 value, while the t1/2 value of telmisartan, which exhibited the highest CLt value, might be enhanced by the significantly high Vss value, indicating extensive distribution into the tissue compartment (Stangier et al. 2000b). According to the t1/2 values, valsartan should be administered once or twice daily (Anand et al. 2010), and telmisartan should be administered orally once daily (McClellan and Markham 1998) in clinical practice.
Blood pressure targets and pharmacotherapy for hypertensive patients on hemodialysis
Published in Expert Opinion on Pharmacotherapy, 2020
Takashi Maruyama, Hiroyuki Takashima, Masanori Abe
An observational study found no significant difference in all-cause or cardiovascular mortality between patients who were initiated on an ACEI or ARB [98]. The same study then analyzed the results in patients who required another antihypertensive medication in addition to an ACEI or ARB (i.e., an ACEI + ARB group, an ACEI + other antihypertensive group, and an ARB + other antihypertensive group). The risk of cardiovascular death was found to be highest in the ACE + ARB group and lowest in the ARB + other antihypertensive. Interestingly, ACEI + ARB therapy had beneficial effects on survival in patients with a history of coronary artery disease, myocardial infarction, or severe chronic heart failure [98]. In a further study, 332 patients on hemodialysis who had reduced LVEF (<40%) and had already been treated with ACEIs were randomly divided into an add-on ARB telmisartan group or a placebo group in a double-blind manner [99]. Telmisartan reduced cardiovascular mortality and hospitalizations for worsening chronic heart failure after a mean follow-up of 35.5 months. A recent meta-analysis revealed that a combination of two different RAAS inhibitors (an ACEI plus an ARB or spironolactone plus an ACEI/ARB) decreased all-cause mortality to a greater extent than RAAS monotherapy in a dialysis population [100]. However, there was no significant between-group difference in the cardiovascular mortality rate.
Cubosomal based oral tablet for controlled drug delivery of telmisartan: formulation, in-vitro evaluation and in-vivo comparative pharmacokinetic study in rabbits
Published in Drug Development and Industrial Pharmacy, 2019
Mohamed Yasser, Mahmoud Teaima, Mohamed El-Nabarawi, Rehab Abd El-Monem
Telmisartan (TEL) is an antihypertensive drug classified as a non-peptide angiotensin-II receptor (type AT1) blocker. It lessens the vasoconstrictor and aldosterone-emitting impacts of angiotensin-II by particularly obstructing its signaling to the AT1 receptor in adrenal gland and smooth muscles vasculature. TEL demonstrates an inadequately water-dissolution behavior which constrains its penetration through lipid bilayer layers in humans and animals. It is delegated a class II drug having a low aqueous solubility. Many attempts have been employed in order to improve the solubility and dissolution rate of TLM such as solid dispersion [23,24] and complexation [25]. B-cyclodextrin nanocomposites of TLM were prepared using mechanical grinding, which increased the dissolution rate of the drug. Telmisartan nanodispersion prepared by spray drying method with water soluble polymer without adding surfactant or alkali solubilizer was also another successful trial [26].The marketed products are formulated based on the use of strong alkalinizers such asalkali, meglumine, or combination of them as pH modulators increasing the microenvironmental pH creating a suitable conditions for optimum solubility required for absorption. However, this leads to distortion of the small intestine mucosal tissues [27]. For this reason, our study focused on formulation and assessment of TEL cubosomes in an attempt to resolve the bioavailability problem without affecting patient physiological environment. The pharmacokinetic parameters of the studied samples will be evaluated after oral administration to male albino rabbits as model animals.