Alogliptin And Pioglitazone

Alogliptin And Pioglitazone Uses, Dosage, Side Effects, Food Interaction and all others data.

Alogliptin is a selective, orally-bioavailable inhibitor of enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt and exists predominantly as the R-enantiomer (>99%). It undergoes little or no chiral conversion in vivo to the (S)-enantiomer. FDA approved January 25, 2013.

Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval.

Pioglitazone is a preparation of Pioglitazone which is a member of the newest class of oral antidiabetic agent called thiazolidinediones. It depends on the presence of Insulin for its mechanism of action. Pioglitazone decreases Insulin resistance in the periphery and in the liver, resulting in increased Insulin dependent glucose disposal and decreased hepatic glucose output. It also improves abnormality in lipid metabolism by activating peroxisome proliferator activated receptor gamma (PPAR-γ).

Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves impaired glucose homeostasis. In patients with type 2 diabetes mellitus, these effects result in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values.

Significant fluid retention leading to the development/exacerbation of congestive heart failure has been reported with pioglitazone - avoid its use in patients in heart failure or at risk of developing heart failure. There is some evidence that pioglitazone may be associated with an increased risk of developing bladder cancer. Pioglitazone should not be used in patients with active bladder cancer and should be used with caution in patients with a history of bladder cancer.

Alogliptin And Pioglitazone
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Alogliptin And Pioglitazone
Generic	Alogliptin + pioglitazone
Weight	12.5mg + 15mg, 12.5mg + 30mg, 12.5mg + 45mg, 25mg + 15mg, 25mg + 30mg, 25mg + 45mg
Type	Oral tablet
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Alogliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used to treat hyperglycemia in patients with type 2 diabetes mellitus.

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Pioglitazone is used for an adjunct to diet and exercise to improve glycaemic control in patients with type II diabetes (NIDDM). Pioglitazone is used for monotherapy and also used for use in combination with sulphonylurea, Metformin or Insulin when diet and exercise plus the single agent does not result in adequate glycaemic control.

Alogliptin And Pioglitazone is also used to associated treatment for these conditions: Type 2 Diabetes MellitusDiabetes, Diabetic Neuropathies, Type 2 Diabetes Mellitus

How Alogliptin And Pioglitazone works

Alogliptin inhibits dipeptidyl peptidase 4 (DPP-4), which normally degrades the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide 1 ( GLP-1). The inhibition of DPP-4 increases the amount of active plasma incretins which helps with glycemic control. GIP and GLP-1 stimulate glucose dependent secretion of insulin in pancreatic beta cells. GLP-1 has the additional effects of suppressing glucose dependent glucagon secretion, inducing satiety, reducing food intake, and reducing gastric emptying.

Pioglitazone is a selective agonist at peroxisome proliferator-activated receptor-gamma (PPARγ) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARγ increases the transcription of insulin-responsive genes involved in the control of glucose and lipid production, transport, and utilization. Through this mechanism, pioglitazone both enhances tissue sensitivity to insulin and reduces the hepatic production of glucose (i.e. gluconeogenesis) - insulin resistance associated with type 2 diabetes mellitus is therefore improved without an increase in insulin secretion by pancreatic beta cells.

Dosage

Alogliptin And Pioglitazone dosage

Pioglitazone can be taken once daily without regard to meals. The management of antidiabetic therapy should be individualized. Pioglitazone monotherapy may be initiated at 15 mg or 30 mg once daily dosages in patients not adequately controlled with diet and exercise alone. For patients who respond inadequately to the initial dose of Pioglitazone, the dose can be increased up to 45 mg once daily. For patients not responding adequately to monotherapy, combination therapy should be considered.

Maximum recommended daily dose of Pioglitazone should not exceed 45 mg since doses higher than 45 mg have not been studied in placebo controlled clinical studies. Besides, no placebo controlled clinical studies of more than 30 mg once daily have been conducted in combination therapy.

Side Effects

The overall incidence and types of adverse events reported in placebo controlled clinical trials of Pioglitazone monotherapy at doses of 7.5 mg, 15 mg, 30 mg or 45 mg once daily are upper respiratory tract infection (13.2%), headache (9.1%), sinusitis (6.3%), myalgia (5.4%), tooth disorder (5.3%), and pharyngitis (5.1%).

Toxicity

Common adverse reactions (reported in ≥4% of patients treated with alogliptin 25 mg and more frequently than in patients who received placebo) are: nasopharyngitis, headache, and upper respiratory tract infection.

The oral TDLo observed in mice is 24 mg/kg for 4 days and for rats is 3 mg/kg for 6 days.

One instance of overdose was reported during clinical trials with pioglitazone in which a patient took an oral dose of 120mg daily for four days, followed by 180mg daily for seven days - this patient did not report any adverse clinical symptoms during this time. In the event of overdosage, employ symptomatic and supportive measures according to the patient's clinical status.

Precaution

Pioglitazone exerts its antihyperglycaemic effect only in the presence of Insulin. Therefore, it should not be used in Type 1 diabetes or for the treatment of diabetic ketoacidosis. Pioglitazone should be used with caution in case of combination antidiabetic therapy and hepatic insufficiency. Liver enzyme should be monitored regularly.

Interaction

Administration of thiazolidinediones with an oral contraceptive containing ethinyl oestradiol and norethindrone reduces the plasma concentration of both hormones by approximately 30% which could result in loss of contraception.

Volume of Distribution

Following a single, 12.5 mg intravenous infusion of alogliptin to healthy subjects, the volume of distribution during the terminal phase was 417 L, indicating that the drug is well distributed into tissues.

The average apparent volume of distribution of pioglitazone is 0.63 ± 0.41 L/kg.

Elimination Route

The pharmacokinetics of NESINA was also shown to be similar in healthy subjects and in patients with type 2 diabetes. When single, oral doses up to 800 mg in healthy subjects and type 2 diabetes patients are given, the peak plasma alogliptin concentration (median Tmax) occurred 1 to 2 hours after dosing. Accumulation of aloglipin is minimal. The absolute bioavailability of NESINA is approximately 100%. Food does not affect the absorption of alogliptin.

Following oral administration of pioglitazone, peak serum concentrations are observed within 2 hours (T_max) - food slightly delays the time to peak serum concentration, increasing T_max to approximately 3-4 hours, but does not alter the extent of absorption. Steady-state concentrations of both parent drug and its primary active metabolites are achieved after 7 days of once-daily administration of pioglitazone. C_max and AUC increase proportionately to administered doses.

Half Life

Terminal half-life = 21 hours

The mean serum half-life of pioglitazone and its metabolites (M-III and M-IV) range from 3-7 hours and 16-24 hours, respectively.

Clearance

Renal clearance = 9.6 L/h (this value indicates some active renal tubular secretion); Systemic clearance = 14.0 L/h.

The apparent clearance of orally administered pioglitazone is 5-7 L/h.

Elimination Route

Renal excretion (76%) and feces (13%). 60% to 71% of the dose is excreted as unchanged drug in the urine.

Approximately 15-30% of orally administered pioglitazone is recovered in the urine. The bulk of its elimination, then, is presumed to be through the excretion of unchanged drug in the bile or as metabolites in the feces.

Pregnancy & Breastfeeding use

Pregnancy: There are no adequate and well controlled studies in pregnant women. Pioglitazone should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Lactation: It is not known whether Pioglitazone is secreted in human milk. As many drugs are excreted in human milk, it should not be administered to a lactating women.