8 research outputs found
Synergistic effect of combining theophylline and drugs that potentially elevate serum creatine kinase
An increase in the serum creatine kinase (CK) level is one of the side effects of theophylline;on rare occasions, the increase may be followed by rhabdomyolysis. Theophylline is often administered with drugs that potentially elevate the serum CK level (CK-elevating drugs) such as β-agonists and steroids. However, the effects of the combined treatment of theophylline and CK-elevating drugs have not been reported. We, therefore, retrospectively investigated the effects of combined treatment on the serum CK level, in391asthmatic outpatients.
In this study, the number and type of the CK-elevating drugs administered, and the serum levels of CK and theophylline, were investigated. The patients were divided into four groups:the theophylline-treated and CK-elevating drug-treated group, the theophylline-treated and non-CK-elevating drug-treated group, the non-theophylline-treated and CK-elevating drug-treated group, and the non-theophylline-treated and non-CK-elevating drug-treated group.
The theophylline-treated and CK-elevating drug-treated group showed about 100%higher serum CK levels (225IU/L) than any other group (102-124IU/L), and no increase in the serum theophylline level. This result indicates that there is a synergistic effect of theophylline and CK-elevating drugs on the serum CK level.
The combined treatment of theophylline and CK-elevating drugs induces a synergistic increase in the serum CK level, indicating not pharmacokinetic but pharmacodynamic interactions with these drugs
One-Step Conjugation Method for Site-Specific Antibody–Drug Conjugates through Reactive Cysteine-Engineered Antibodies
Engineered cysteine residues are
particularly convenient for site-specific
conjugation of antibody–drug conjugates (ADC), because no cell
engineering and additives are required. Usually, unpaired cysteine
residues form mixed disulfides during fermentation in Chinese hamster
ovarian (CHO) cells; therefore, additional reduction and oxidization
steps are required prior to conjugation. In this study, we prepared
light chain (Lc)-Q124C variants in IgG and examined the conjugation
efficiency. Intriguingly, Lc-Q124C exhibited high thiol reactivity
and directly generated site-specific ADC without any pretreatment
(named active thiol antibody: Actibody). Most of the cysteine-maleimide
conjugates including Lc-Q124C showed retro-Michael reaction with cysteine
34 in albumin and were decomposed over time. In order to acquire resistance
to a maleimide exchange reaction, the facile procedure for succinimide
hydrolysis on anion exchange resin was employed. Hydrolyzed Lc-Q124C
conjugate prepared with anion exchange procedure retained high stability
in plasma. Recently, various stable linkage schemes for cysteine conjugation
have been reported. The combination with direct conjugation by the
use of Actibody and stable linker technology could enable the generation
of stable site-specific ADC through a simple method. Actibody technology
with Lc-Q124C at a less exposed position opens a new path for cysteine-based
conjugation, and contributes to reducing entry barriers to the preparation
and evaluation of ADC