A Pharmacokinetic/Pharmacodynamic (PK/PD) and Safety Evaluation of Oseltamivir [Tamiflu] in the Treatment of Infants 0 to <12 Months of Age With Confirmed Flu Infection

Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 was estimated for oseltamivir and oseltamivir carboxylate by linear trapezoidal rule

Oseltamivir carboxylate is an active metabolite of oseltamivir. Cmax was estimated for both oseltamivir and Oseltamivir carboxylate by non-compartmental analysis.

Oseltamivir carboxylate is active metabolite of oseltamivir. Cmin was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis

Oseltamivir carboxylate is an active metabolite of oseltamivir.Tmax was estimated using non-compartmental methods

Elimination half-life is defined as the time required for elimination of a drug to half its plasma concentration and was computed using non-compartmental method

Oseltamivir carboxylate is active metabolite of oseltamivir.The apparent first-order elimination rate constant (Lambda Z) was determined by linear regression analysis of terminal data points. A minimum of 3 data points were used for lambda Z estimation. By reporting tool convention, if n<3, no summary statistics were calculated

Oseltamivir carboxylate is active metabolite of oseltamivir. CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity

Oseltamivir carboxylate is active metabolite of oseltamivir. V/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

The last measurable plasma concentration of oseltamivir and oseltamivir carboxylate was the last quantifiable concentration of oseltamivir or oseltamivir carboxylate, respectively.

Oseltamivir carboxylate is an active metabolite of oseltamivir.

Neurological assessment was performed to assess the mental state of the participants through two scales: Infant face scale and Glasgow coma scale. Each scale consists of 3 subscales: eye opening (ranging 1 to 4), verbal response (ranging 1 to 5), and motor responses (ranging 1 to 6). The final score is the sum of these ranges and is scored between 3 and 15. 3 being the worst, and 15 the best. Change from baseline is change of final score post-baseline minus the final score at baseline.

Median time to cessation of viral shedding was calculated for all patients with positive by culture / by polymerase chain reaction (PCR) at baseline using all data points between the start of the treatment and the 1st time point of negative culture without subsequent positive culture results. These time-to event analyses were only performed for the viral titre.

The viral titer was measured by culture and reported in log10 (50% tissue culture infective dose [TCID50]). The viral load was analyzed by PCR and reported as log10 particles/mL. The number of patients positive for viral shedding by virus sub-type was measured on specified days from baseline to last visit on Day 30.

This was performed for all participants who had fever at baseline. Fever is defined as body temperature >37.0 degree Celsius. Rectal temperature is converted by subtracting 1 degree Celsius. Time to Resolution of Fever was defined as the time from the initiation of treatment to first time the afebrile state was reached and maintained for at least 21.5 hours, where afebrile state was defined as axillary temperature ≤ 37 degree Celsius.

This was performed for all participants who had fever at baseline Fever is defined as body temperature >37.0ºC. Rectal temperature is converted by subtracting 1 ºC. The rate of decline of body temperature was calculated as the slope of body temperature between the baseline temperature and the 1st temperature below 37°C. Participants with decline in body temperature were considered to have no fever; however, participants who did not show any decline in body temperature were considered to have persisting fever.

An Adverse Event (AEs) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. Secondary illnesses were influenza disease-related events, namely bronchitis, pneumonia, otitis media, and sinusitis that resolved without sequelae. Adverse events, serious adverse events, and secondary illness are reported for on-treatment period (from the first dose of oseltamivir upto 3 days after the last dose of oseltamivir [Approximately 14 days].

Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and heart rate were examined for any consistent within-patient post-baseline changes.