Antibiotic resistance is a critical medical issue. Antiseptics, which play a key role in treating and preventing eye infections and inflammations, have the potential to induce resistance in pathogenic microorganisms despite their broad antimicrobial spectrum. When introducing new active substances into ophthalmic treatments, it is crucial to assess the risk of side effects caused by the systemic action of the active compound. The succinic salt of polyhexamethylene guanidine derivative (ss-PHMGd) has shown high in vitro activity. This study aimed to evaluate the systemic effects of ss-PHMGd-based eye drops after ocular instillation in a preclinical model. Simple mathematical models were used to calculate pharmacokinetic parameters during instillation in two types of laboratory animals: guinea pigs and chinchilla rabbits. Groups received intravenous injections and ocular treatments. Tritium-labeled ss-PHMGd was used to quantify its concentration in organs and tissues. To test the linearity of the parameter relationships, data from three different doses were compared. Renal excretion was studied by quantifying ss-PHMGd concentrations in urine using radiometric methods. The results showed that ss-PHMGd-based eye drops present a low risk of systemic side effects and exhibit minimal penetration into other organs after instillation. No species-specific differences were found in the ADME parameters of the preclinical models (the guinea pig-to-chinchilla rabbit absorption ratio was 0.7). The AUC-D parameters exhibited a linear relationship for doses ranging from 0.5 of therapeutic dose (TD) to 5TD in guinea pigs. Renal excretion analysis revealed that 5.3% of the administered dose was excreted through the kidneys, indicating significant metabolic transformation or excretion via other pathways. This study enhances the understanding of the pharmacokinetics and safety of polyguanidines, with implications for toxicology and risk assessment.

There is still a considerable burden of occupational diseases and injuries in the world. It is not well known which interventions can effectively reduce the exposures at work that cause this burden. The objective of this article is to summarize evidence from systematic reviews of interventions to prevent occupational diseases and injuries. We included systematic reviews of interventions to reduce the incidence of work-related cancer, dust-related diseases, occupational asthma, chronic obstructive pulmonary disease, noiseinduced hearing loss, back pain, and occupational injuries. We searched Medline and Embase with predefined search strategies to locate systematic reviews of these interventions. We found 23 systematic reviews of which the results are also applicable to low- and middle income countries. Effective measures to reduce exposure leading to work-related cancer, dust-related diseases, asthma, chronic obstructive pulmonary disease, noise, and injuries are available. However, better implementation of these measures is needed. Regulation, enforcement of regulation, and incentives for employers are effective interventions to achieve this goal. There is evidence that feedback and rewards for workers help in reducing occupational injuries. There is no evidence in many studies that back pain can be prevented. Personal protective equipment technically has the potential to reduce exposure but this is difficult to put into effect. There is no evidence in the studies regarding the effectiveness of education and training, preventive drugs, or health examinations. There is evidence that the implementation of technical measures enforced by regulation can prevent occupational diseases and injuries. For other interventions such as education or health examinations, there is no evidence that supports their effectiveness. More systematic reviews are needed in the area of injury prevention.
Asthma ; Back Pain ; Education ; Hearing Loss ; Humans ; Incidence ; Clinical Trial ; Motivation ; Noise ; Occupational Diseases ; Occupational Health* ; Occupational Injuries ; Pulmonary Disease, Chronic Obstructive ; Reward