Long-Acting Injectable Statins—Is It Time for a Paradigm Shift?

Abstract

In recent years, advances in pharmaceutical processing technologies have resulted in development of medicines that provide therapeutic pharmacokinetic exposure for a period ranging from weeks to months following a single parenteral administration. Benefits for adherence, dose and patient satisfaction have been witnessed across a range of indications from contraception to schizophrenia, with a range of long-acting medicines also in development for infectious diseases such as HIV. Existing drugs that have successfully been formulated as long-acting injectable formulations have long pharmacokinetic half-lives, low target plasma exposures, and low aqueous solubility. Of the statins that are clinically used currently, atorvastatin, rosuvastatin, and pitavastatin may have compatibility with this approach. The case for development of long-acting injectable statins is set out within this manuscript for this important class of life-saving drugs. An overview of some of the potential development and implementation challenges is also presented.

Pharmacokinetic analysis of two different doses of simvastatin following oral administration in dogs

“…Reportedly, the half‐maximal inhibitory concentration of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase for simvastatin is 1–2 nmol/L (Sirtori, 2014). Although simvastatin has highly plasma protein binding (>90%), the plasma target concentration for the drug in humans has been demonstrated to be 1.4 ng/ml based on trough concentration ( C trough ) under the clinical dose regimen (Sunkara et al., 2007; Tatham et al., 2019). Although the pharmacological mechanism and plasma target concentration of simvastatin would differ between dogs and humans, our study can be helpful in optimizing the dosage regimen for canine hypercholesterolemia in veterinary medicine.…”

Polymer–prodrug conjugates as candidates for degradable, long-acting implants, releasing the water-soluble nucleoside reverse-transcriptase inhibitor emtricitabine

“…The benefits to patients are considerable, including minimising the impact of daily oral tablet dosing on lifestyle, but carers and clinicians are better able to ensure adherence to therapy with resulting improvements in efficacy and outcomes. [13][14][15][16] Unmet healthcare needs span areas such as chronic infection, cardiovascular health, psychosis treatments and prevention of life-threatening diseases such as malaria, hepatitis and tuberculosis. 17 Human immunodeficiency virus (HIV) infection requires a lifelong commitment to daily dosing of a combination of antiviral drug compounds.…”