Drug discovery and development is a long process: it takes usually 12 to 15 years before a drug candidate reaches the market. The pharmacokinetics of the drug is an important aspect of drug discovery and development, because the drug must reach its target site and exert the therapeutic response. The pharmacokinetic parameters of new compounds should be investigated early in drug discovery. Pharmacokinetic predictions can be made with Quantitative Structure-Property Relationships (QSPR) which are computational models that correlate chemical features with pharmacokinetic properties. The correlations are based on in vivo or in vitro pharmacokinetic data and molecular descriptors. QSPR models can be used to predict the pharmacokinetic parameters even before any actual drug synthesis and can be exploited to guide drug discovery. Pharmacokinetic models can also simulate concentration profiles of drugs during the drug discovery and development process. It was decided to develop QSPR models of pharmacokinetic parameters of drugs to be delivered by the systemic or ocular routes. A combination of Principal Component Analysis and Partial Least Square multivariate statistical methods was used to obtain QSPR equations for volume of drug distribution and fraction of unbound drug in plasma. Parallel modelling of these parameters resulted in acceptable R2 (0.58 - 0.77) and Q2 values (0.55 - 0.58). These models are based on a large set of structurally unrelated compounds, they are open and they have a defined applicability domain. Charge and lipophilicity related descriptors were the relevant ones which influenced the volume of distribution and free fraction of drug in plasma. Pharmacokinetics is an important factor in the development of ocular medications, because the ocular drug targets are difficult to reach, particularly in the posterior tissues such as retina and choroid. Therefore, drugs need to be injected intravitreally in the treatment of retina and choroid diseases (e.g. in exudative age-related macular degeneration) and thus prediction of intravitreal pharmacokinetics would be especially advantageous in ocular drug discovery and development. The first comprehensive collection of intravitreal volume of distribution and clearance values of compounds was collated based on extensive rabbit eye data from the literature. Moreover, predictive QSPR models for intravitreal clearance and half-life were created which had R2 and Q2 values of 0.62 0.84 for clearance and 0.61 - 0.80 for half-life. LogD7.4 and hydrogen bonding capacity defined the intravitreal clearance and half-life of compounds with a molecular weight below 1500 Da. The intravitreal volumes of drug distribution lay within a narrow range (80% within 1.18 - 2.28 ml). The QSPR models for intravitreal clearance and the typical values for intravitreal volumes of distribution were implemented in pharmacokinetic simulation models; the simulated profiles based on the real and predicted pharmacokinetic parameter values were similar. Thus, a combination of QSPR and pharmacokinetic models can be used in drug discovery and development to aid in the design of drugs and drug delivery systems. A comprehensive comparison of intravitreal pharmacokinetic data between rabbit and human was carried out to clarify the translational value of the rabbit model. The analysis revealed that the rabbit can be considered as a clinically predictive animal model for intravitreal pharmacokinetics of small molecules (18 Da - 1500 Da) and macromolecules (7.1 kDa - 149 kDa). There was a correlation between the intravitreal clearance values in human patients and healthy rabbits; they showed similar, but not identical, absolute values. The intravitreal pharmacokinetics of small molecules is mainly governed by permeability-limited clearance across blood-ocular barriers and occurs via the posterior route, whereas large molecules are cleared mostly via the anterior route. Although the literature contains some claims about the significance of the viscosity of the vitreous, it seems that this is not a major factor in drug elimination from the eye. In conclusion, new in silico tools were generated for systemic and ocular pharmacokinetics and drug delivery. These models can be exploited in industrial drug discovery and will hopefully speed up the development of new medications.Silmätaudeissa lääkehoitoa vaikeuttaa se, että lääkehoitoa on vaikea saattaa perille silmänpohjaan verkkokalvon soluihin, joissa näkövammaisuuteen ja sokeutumiseen johtavat muutokset tavallisesti tapahtuvat. Näin ollen lääkkeitä joudutaan antamaan silmän sisään toistuvina injektioina esimerkiksi verkkokalvon ikärappeuman hoidossa. Lääkkeiden kulkeutumisen ymmärtäminen ja ennustaminen tietokoneella auttaa pitkävaikutteisten injektioiden ja vaihtoehtoisten lääkkeen antotapojen kehittämistä. Väitöskirjassa kehitettiin tällaisia tietokonemalleja pohjautuen julkaistuihin tutkimuksiin
