Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam.

AIM: This phase I, multicentre, open-label, nonrandomised, parallel-group, two-part study aimed to evaluate the effect of mild to moderate hepatic impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of risdiplam. METHODS: Adult subjects (aged 18-70 years) with mild (Child-Pugh Class A; Part 1) or moderate (Child-Pugh Class B; Part 2) hepatic impairment were matched with subjects with normal hepatic function on sex, age, body mass index and smoking status. Each subject received a single oral dose of 5 mg of risdiplam. Plasma concentrations of risdiplam and its metabolite M1 were measured and PK parameters were compared. Adverse events, laboratory abnormalities, vital signs and electrocardiogram measurements were assessed. RESULTS: After a single dose (5 mg) of risdiplam, the risdiplam PK parameters area under the plasma concentration-time curve from time zero to infinity and maximum observed plasma concentration were approximately 20% and 5% lower, respectively, in subjects with mild hepatic impairment and approximately 8% and 20% higher, respectively, in subjects with moderate hepatic impairment compared with subjects with normal hepatic function. These differences were not statistically significant; all 90% confidence intervals for geometric least squares-means ratios spanned unity. No new risdiplam-related safety findings were observed in subjects with mild or moderate hepatic impairment. CONCLUSION: Mild or moderate hepatic impairment did not have a clinically relevant impact on the PK of risdiplam. Therefore, no dose adjustment is required in patients with mild or moderate hepatic impairment when receiving risdiplam.

Sacrococcygeal pilonidal disease: sinotomy versus excisional surgery, a retrospective study.

Pilonidal disease is a disease of relatively young people, the exact aetiology of which is unknown. Treatment options vary from simple incision to complex flap procedures. Each method has its advocates and they all have a variable recurrence rate. The multiplicity of procedures testifies to the lack of an optimal treatment method. The objective of this study is to compare sinotomy, that is, simply laying the sinus open with the more popular radical surgery, where the sinus-bearing tissues are excised. Patients who were admitted to Aseer Central Hospital, Saudi Arabia with a pilonidal sinus or abscess, in the period from April 1999 to January 2005, were identified. The medical records were reviewed and data related to the patient characteristics, disease process and the procedures carried out were noted. Identified patients were contacted by phone to check recurrence of the disease and their abidance to instructions regarding regular hair removal from the area. Eighty-one patients were included in the study. The median age was 24.2 years (range 16-60 years). There were 9 women and 72 men. All procedures were carried out under general anaesthesia except sinotomy, which was carried out under general or local anaesthesia. The surgical procedure was incision and drainage of abscess in 16 cases (19.8%), excision with primary closure in 29 cases (35.8%), excision by the open method in 15 cases (18.5%), sinotomy in 14 cases (17.3%) and rhomboid flap construction in 8 cases (9.9%). The overall recurrence rate was 26.9%, and the mean hospital stay was 4.1 days. Sinotomy had a low recurrence rate (12.5%) and a short hospital stay (2.8 days). Sinotomy has the advantages of simplicity, the possibility of operating under local anaesthesia, with an acceptable recurrence rate. We recommend sinotomy for pilonidal sinus and abscess alike, both in primary and recurrent cases.