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Recurrent pregnancy loss (RPL) represents a complication of pregnancy occurring in 1%-3% of all couples trying to conceive. About 50%-60% of RPL cases remain idiopathic, therefore therapeutic strategies seem empirical and based on unproven evidence. We investigated the efficacy of corticosteroids in women with RPL.

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Cyclodextrin Inclusion Complexes with Hydrocortisone-Type Corticosteroids.

Pharmaceutics

December 2024

Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Str., 02-093 Warsaw, Poland.

The hydrocortisone-type corticosteroid (HTC) group includes valuable active pharmaceutical ingredients (APIs) such as hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, and prednisone. Unfortunately, those APIs are characterized by low solubility, which hampers their application and reduces their therapeutic efficacy. The low polarity of HTC molecules allows them to form inclusion complexes with various cyclodextrins (CDs); however, as shown in this review, the type of applied CDs has a major impact on the final properties of the formed complex.

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Objective: Traditional initial treatment regimens for lupus nephritis (LN) used oral glucocorticoids (GC) in starting doses up to 1.0 mg/kg/day prednisone equivalent with or without a preceding intravenous methylprednisolone pulse. More recent management guidelines recommend lower starting oral GC doses following intravenous pulse therapy.

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Background And Purpose: The main features of the dynamics of the glucocorticoid receptor (GR) have been known for 50 years: 1) in the absence of glucocorticoid (G), the receptor is localized entirely in the cytoplasm; 2) upon G binding, GR is converted into a tightly bound G form and is rapidly imported into the nucleus where it can bind DNA and modulate transcription; 3) nuclear export of GR is very slow; and 4) the nuclear form of GR can recycle through an unbound form, back to the bound transcription modulating form without leaving the nucleus.

Experimental Approach: A kinetic model that captures these features is presented, a set of model parameters for dexamethasone is derived, and the clinical implication for the commonly used glucocorticoids is discussed.

Key Results: At the high concentrations normally used to describe G pharmacodynamics, the model reduces to the standard Michaelis-Menten equation with a that is a function of 4 model parameters.

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